Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present stud...Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.展开更多
As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but t...As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.展开更多
Objective Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CY...Objective Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE). Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.展开更多
Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine prote...Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.展开更多
We investigated relationship between galectin-3 (Gal-3) levels and T lymphocytes apoptosis and the activation rates in breast cancer during chemotherapy. We used plasma samples from 112 women classified into two group...We investigated relationship between galectin-3 (Gal-3) levels and T lymphocytes apoptosis and the activation rates in breast cancer during chemotherapy. We used plasma samples from 112 women classified into two groups: 70 women with breast cancer (BC) and submitted to neoadjuvant chemotherapy (3 cycles) and 42 healthy women used as controls. In the group of BC, blood samples were taken before each cycle of chemotherapy and Gal-3 levels was evaluated by ELISA sandwich. Flow cytometry was used to study T cells apoptosis and activation. Before treatment, median value of Gal-3 was 6.31 ng/ml (range 1.07 - 50.74) in BC and 0.84 ng/ml (range 0.00 - 4.82) in HC. Gal-3 levels were highest in plasmas from BC (p p p = 0.010). In addition, we found a dynamic relationship between gal-3 levels, tumor size and T lymphocytes apoptosis rates during treatment depending to the cure efficiency. We suggest gal-3 plasma concentrations could be used as predictive biomarker for chemotherapy efficiency in breast cancer patients.展开更多
BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diag...BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.展开更多
BACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from ...BACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from the gut. Yet, the route of bacterial translocation into the bile duct is still unclear. Theoretically, two routes exist: one is through the intestinal barrier and the other is by direct reflux from the sphincter of Oddi. This study was undertaken to explore the relationship between the effectiveness of intestinal barrier and the formation of pigment gallstones in hamsters. METHODS: Thirty-two hamsters were divided into an experimental and a control group, with 16 hamsters in each group. A low protein and high cellulose diet was given for 6 weeks to induce the formation of pigment gallstones in the experimental group (PS) and a normal diet was given to the control group (CON). Morphological changes, changes in the levels of serum endotoxin and diamine oxidase, and changes in the numbers of B lymphocytes, plasma cells and secretory immunoglobin A (sIgA) in the intestinal mucosa were assessed after 6 weeks. RESULTS: Four hamsters died during lithogenesis and body weight decreased in the PS group. Pigment gallstones were found in 11 hamsters at the end of the experiment, giving a lithogenesis rate of 91.67%. The serum endotoxin level before and after gallstone formation in the PS group was 0.2960 +/- 0.1734 U/ml and 8.2964 +/- 4.6268 U/ml, respectively (P<0.05). The blood diamine oxidase level before and after gallstone formation in the PS group was 2.6333 +/- 0.8037 U/ml and 3.3642 +/- 0.9545 U/ml, respectively (P<0.05). The numbers of B lymphocytes, plasma cells and sIgA in the intestinal mucosa in the PS group were 71.56 +/- 2.89, 68.65 +/- 2.09 and 27.56 +/- 1.07, respectively, and were significantly decreased compared with the corresponding values in the CON group (94.25 +/- 3.69, 93.47 +/- 3.98 and 42.57 +/- 1.96, respectively, P<0.05). CONCLUSIONS: A low protein and high cellulose diet can markedly reduce intestinal barrier function and facilitate the formation of pigment gallstones. The decrease of intestinal barrier function may take part in the formation of pigment gallstones.展开更多
Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to ex...Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.展开更多
Bispecific antibodies (BsAbs) of anti CD3×anti idiotype (Id) to B cell lymphocytic leukemia (CLL) were prepared by chemical conjugation and direct hybridization technique of hybridoma and hybridoma without scr...Bispecific antibodies (BsAbs) of anti CD3×anti idiotype (Id) to B cell lymphocytic leukemia (CLL) were prepared by chemical conjugation and direct hybridization technique of hybridoma and hybridoma without screening markers. The specificity of BsAbs from culture supernatants or ascites was assayed by indirect ELISA and indirect immunoflurescence (IF). The results showed that BsAbs could specifically react with homologous serum IgM from patients with B CLL and cells carrying CD3 marker respectively. Cell combination test and LDH assay demonstrated that BsAb significantly increased the conjugate formation between lymphocyte activated kill (LAK) cells and Daudi cells, and enhanced the cytotoxic activity of LAK cells against Daudi cells.展开更多
The expression vector of SmIg scFv fragment was constructed in patient with B cell chronic lymphocyte leukemia (B-CLL) and expressed in E. coli to obtain scFv fragment, and the effect of the protein on the prolifera...The expression vector of SmIg scFv fragment was constructed in patient with B cell chronic lymphocyte leukemia (B-CLL) and expressed in E. coli to obtain scFv fragment, and the effect of the protein on the proliferation of stimulated peripheral blood mononuclear cells (PBMC) was investigated in vitro. Two pairs of primers were designed, and variable region genes of light chain and heavy chain were amplified by PCR respectively from the pGEM-T vectors previously constructed in our laboratory which containing light chain gene or Fd fragment of heavy chain gene. The PCR product was digested, purified and inserted into pHEN2 vector to construct the soluble expression vector pHEN2-scFv. After the induction by IPTG, the scFv protein was identified by SDS- PAGE electrophoresis and purified by Ni-NTA-Chromatography. MTT was used to determine the effect of purified protein on the proliferation of stimulated PBMC in vitro. Plasmid PCR and restriction enzyme digestion of pHEN2-scFv revealed the pHEN2-scFv vector was constructed successfully. Id-scFv protein was expressed in positive clone after induced by IPTG. SDS-PAGE analysis showed that the relative molecular weight of fusion protein was about 30 kD (1 kD= 0. 9921 ku), which was consistent with the theoretically predicted value. Proliferation of PBMC could be induced by purified Id-scFv. It was suggested that the expression vector of SmIg scFv fragment was constructed successfully, and scFv protein was expressed and secreted from E. coil, which could induce proliferation of PBMC. This may lay an experimental foundation for further research of Id- HSP complex vaccine for B-CLL.展开更多
Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2...Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2 % difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post GC cells.展开更多
A double antibodies additivity ELISA test was employed to identify the epltopes which can be recognized by monoclonal antibodies (McAbs) against IgM from B chronic lymphocyte leukemia (B-CLL). The computer grouping pr...A double antibodies additivity ELISA test was employed to identify the epltopes which can be recognized by monoclonal antibodies (McAbs) against IgM from B chronic lymphocyte leukemia (B-CLL). The computer grouping programme analysis showed that 4 and- isotypic MaAbs could be divided into two groups and 10 anti- idiotype McAbs could be divided into four groups. The result was consistent with that of the indirect sandwich ELISA and inhibition ELISA test. It suggested that there were at least 6 distinct IgM epitopes which can react specifically with 14 McAbs. Our study indicated that the combination of the additivity ELISA test and the computer grouping programme analysis is of help in studying the relationship of the structure and function of antigen.展开更多
End-stage kidney failure(ESKD)is a global issue where kidney replacement therapy imposes enormous economic burden to people of developing countries,in addition to the severe limitations to the availability of hemodial...End-stage kidney failure(ESKD)is a global issue where kidney replacement therapy imposes enormous economic burden to people of developing countries,in addition to the severe limitations to the availability of hemodialysis and peritoneal dialysis technique.The best option of kidney transplantation also requires lifelong combination immunosuppressive medicines,the cost of which is equally comparable to lifelong dialysis.A strategy of achieving transplant tolerance that requires minimum immunosuppressive medicines,although in experimental stage,also requires state-of-art technology with costly medicines and interventions.This is evidently beyond the reach of ESKD patients of developing countries.Hence,globally in developing countries,a need for an innovative but cost-effective tolerance protocol is a burning need for a successful transplant program.In brief,transplant tolerance is defined as a state of donorspecific unresponsiveness to the allograft antigens without the need for ongoing pharmacologic immunosuppression or with a minimal need.Current state-of-art techniques involves:(1)A state of hematological chimera,for complete tolerance;(2)Prope or partial tolerance where immune-reactive T-lymphocytes are inhibited using monoclonal antibodies;and(3)Chimeric antigen receptor for T-regulatory(T-reg)cell therapy using genetically engineered T-reg cells targeting specific Tlymphocyte receptors for inducing anergy.From our real-world experience in transplant management in post-transplant lympho-proliferative disorders(PTLD),we noticed frequently a drastic reduction in the need of immunosuppressive medicines following lympho-ablative therapy for PTLD.We recently published a case study on a real-world experience transplant case where we explained a partial or prope tolerance that developed after lymphocyte ablation therapy,following which the allograft was maintained with low dose dual standard immunosuppressive medicines.Based on this publication,we propose here an innovative tolerance protocol for living related low risk kidney transplantation for developing countries,in this opinion review.展开更多
Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might ...Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. JH-/- mice lack the JHgene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B iymphocytes in a number of immune responses; however, JH-/- mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and JH-/- mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of JH-/- mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the JH-/- animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exDosure in the pulmonary compartment.展开更多
Interferon regulatory factor 4 (IRF4) and IRF8 are critical regulators of immune system development and function. In B lymphocytes, IRF4 and IRF8 have been shown to control important events during their development ...Interferon regulatory factor 4 (IRF4) and IRF8 are critical regulators of immune system development and function. In B lymphocytes, IRF4 and IRF8 have been shown to control important events during their development and maturation including pre-B cell differentiation, induction of B cell tolerance pathways, marginal zone B cell development, germinal center reaction and plasma cell differentiation. Mechanistically, IRF4 and IRF8 are found to function redundantly to control certain stages of B cell development, but in other stages, they function nonredundantly to play distinct roles in B cell biology. In line with their essential roles in B cell development, deregulated expressions of IRF4 and IRF8 have been associated to the pathogenesis of several B cell malignancies and diseases. Recent studies have elucidated diverse transcriptional networks regulated by IRF4 and IRF8 at distinct B cell developmental stages and related malignancies. In this review we will discuss the recent advances for the roles of IRF4 and IRF8 during B cell development and associated diseases.展开更多
Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the r...Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.展开更多
Calcium-sensing receptor(CaSR),which was initially found in the parathyroid gland,is ubiquitously expressed and exerts specifi c functions in multiple cells,including immune cells.CaSR is functionally expressed on neu...Calcium-sensing receptor(CaSR),which was initially found in the parathyroid gland,is ubiquitously expressed and exerts specifi c functions in multiple cells,including immune cells.CaSR is functionally expressed on neutrophils,monocytes/macrophages,and T lymphocytes,but not B lymphocytes,and regulates cell functions,such as cytokine secretion,chemotaxis,phenotype switching,and ligand delivery.In these immune cells,CaSR is involved in the development of many diseases,such as sepsis,cryopyrin-associated periodic syndromes,rheumatism,myocardial infarction,diabetes,and peripheral artery disease.Since its discovery,it has been controversial whether CaSR is expressed and plays a role in immune cells.This article reviews current knowledge of the role of CaSR in immune cells.展开更多
Blymphocyte stimulator (BLyS) is also known as B cell activating factor belonging to the tumor necrosis factor (TNF) family (BAFF), or TNF and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-I).^1-...Blymphocyte stimulator (BLyS) is also known as B cell activating factor belonging to the tumor necrosis factor (TNF) family (BAFF), or TNF and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-I).^1-3 As a member of the TNF family, BLyS plays an important role in B cell development, and has been implicated in autoimmune diseases and B cell malignancies.展开更多
Background BAFF, the B cell activation factor, is a member of the tumor necrosis factor (TNF) ligand family that binds to BCMA, TACI, and BAFF-R. Previous studies have shown that members of the TNF family are detect...Background BAFF, the B cell activation factor, is a member of the tumor necrosis factor (TNF) ligand family that binds to BCMA, TACI, and BAFF-R. Previous studies have shown that members of the TNF family are detected in human placental trophoblast cells, but the expression patterns of BAFF involved in human decidua and the differential expression of BAFF between normal pregnancy and miscarriage are still incompletely documented or unknown. This study was designed to investigate the expression of BAFF and BAFF-R in the trophoblast and decidua of normal early pregnant women and recurrent spontaneous abortion (RSA) patients.Methods Forty-five patients with RSA and 45 normal pregnant women were included in this study. By reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical experiments, we explored the expression of BAFF and BAFF-R in the maternal-fetal interface of normal early pregnant women and RSA patients.Results Analysis by RT-PCR and Western blotting revealed that BAFF was detected in both trophoblast and decidua of all the samples, and the expression level was higher in the tissues of normal early pregnant women (P〈0.05) than that of recurrent spontaneous abortion patients under the same gestational weeks. Messages for BAFF-R were absent. Immunohistochemical experiments showed that expression of BAFF was cell-specific which was localized to villous cytotrophoblast and syncytiotrophoblast cells in trophoblast and to stromal cells in decidua. Whereas BAFF was prominent on the trophoblast and decidua of normal early pregnant women, it was decreased in the tissues of RSA patients.Conclusions BAFF might steer maternal leukocytes away from a harmful immune response and toward a favorable one and play a potentially vital role for successful pregnancy.展开更多
The prevalence of nasopharyngeal cancer (NPC) is high in the southern area of China and some other districts in the world. The pathogenesis of NPC is unclear. It is reported that some microRNAs (miR) are involved ...The prevalence of nasopharyngeal cancer (NPC) is high in the southern area of China and some other districts in the world. The pathogenesis of NPC is unclear. It is reported that some microRNAs (miR) are involved in the progression of NPC. This study aims to investigate the role of miR-21 in the induction of immune tolerance of NPC. In this study, NPC tissue was collected from patients with NPC. Assessment of miR was performed with real time quantitative RT-PCR. Western blotting was used to assess proteins of interleukin 10 and nuclear factor I-A (NFI-A), Immune ceils were analyzed by flow cytometry. The results showed that NPC cell line C666-1 and surgically removed NPC tissue expressed miR-21, which was upregulated by the presence of the Toll-like receptor 3 ligand, Poly h C. Exposure to miR-21 increased the expression of NFI-A and interleukin (IL)-IO in naive B cells. High frequency of IL-10+ B cells was detected in the NPC tissue. The NPC- or miR-21-primed B ceils suppressed cytotoxic CD8+ T cell activities. We conclude that NPC-derived miR-21 induces IL-10+ B ceils; the latter is capable of suppressing CD8+ T-cell activities, miR-21 may be a potential target in the treatment of NPC.展开更多
基金This study was supported by a grant from Beijing Natural Science Foundation(7234399).
文摘Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.
基金supported by 16POST27490032 American Heart Association post-doctoral fellowshipNational Institute of Neurological Disorders and Stroke Exploratory Neuroscience Research Grant R21 NS114836-01A1 (to AC)
文摘As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.
基金supported by the National Natural Science Foundation of China (Grant No: 30671731, 30901168)the Doctoral Program of Higher Education of China (Grant No: 20070286069)
文摘Objective Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE). Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.
基金supported by the National Natural Science Foundation of China(No.81904124)the Scientific Project of Shanghai Sanitation and Health Committee(No.20204Y0191)the projects of Shanghai Science and Technology Commission(No.22Y31920200).
文摘Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.
文摘We investigated relationship between galectin-3 (Gal-3) levels and T lymphocytes apoptosis and the activation rates in breast cancer during chemotherapy. We used plasma samples from 112 women classified into two groups: 70 women with breast cancer (BC) and submitted to neoadjuvant chemotherapy (3 cycles) and 42 healthy women used as controls. In the group of BC, blood samples were taken before each cycle of chemotherapy and Gal-3 levels was evaluated by ELISA sandwich. Flow cytometry was used to study T cells apoptosis and activation. Before treatment, median value of Gal-3 was 6.31 ng/ml (range 1.07 - 50.74) in BC and 0.84 ng/ml (range 0.00 - 4.82) in HC. Gal-3 levels were highest in plasmas from BC (p p p = 0.010). In addition, we found a dynamic relationship between gal-3 levels, tumor size and T lymphocytes apoptosis rates during treatment depending to the cure efficiency. We suggest gal-3 plasma concentrations could be used as predictive biomarker for chemotherapy efficiency in breast cancer patients.
基金Supported by the National Natural Science Foundation of China,No.81700130Nanjing Medical University Science and Technology Development Fund.
文摘BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.
文摘BACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from the gut. Yet, the route of bacterial translocation into the bile duct is still unclear. Theoretically, two routes exist: one is through the intestinal barrier and the other is by direct reflux from the sphincter of Oddi. This study was undertaken to explore the relationship between the effectiveness of intestinal barrier and the formation of pigment gallstones in hamsters. METHODS: Thirty-two hamsters were divided into an experimental and a control group, with 16 hamsters in each group. A low protein and high cellulose diet was given for 6 weeks to induce the formation of pigment gallstones in the experimental group (PS) and a normal diet was given to the control group (CON). Morphological changes, changes in the levels of serum endotoxin and diamine oxidase, and changes in the numbers of B lymphocytes, plasma cells and secretory immunoglobin A (sIgA) in the intestinal mucosa were assessed after 6 weeks. RESULTS: Four hamsters died during lithogenesis and body weight decreased in the PS group. Pigment gallstones were found in 11 hamsters at the end of the experiment, giving a lithogenesis rate of 91.67%. The serum endotoxin level before and after gallstone formation in the PS group was 0.2960 +/- 0.1734 U/ml and 8.2964 +/- 4.6268 U/ml, respectively (P<0.05). The blood diamine oxidase level before and after gallstone formation in the PS group was 2.6333 +/- 0.8037 U/ml and 3.3642 +/- 0.9545 U/ml, respectively (P<0.05). The numbers of B lymphocytes, plasma cells and sIgA in the intestinal mucosa in the PS group were 71.56 +/- 2.89, 68.65 +/- 2.09 and 27.56 +/- 1.07, respectively, and were significantly decreased compared with the corresponding values in the CON group (94.25 +/- 3.69, 93.47 +/- 3.98 and 42.57 +/- 1.96, respectively, P<0.05). CONCLUSIONS: A low protein and high cellulose diet can markedly reduce intestinal barrier function and facilitate the formation of pigment gallstones. The decrease of intestinal barrier function may take part in the formation of pigment gallstones.
基金Fund supported by the Healthcare Technology Plan of Zhejiang Provincial Health Bureau(No.2016KYB292)the Technology Plan of Science and Technology Bureau of Jiaxing,Zhejiang province(No.2016AY23054)~~
文摘Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.
文摘Bispecific antibodies (BsAbs) of anti CD3×anti idiotype (Id) to B cell lymphocytic leukemia (CLL) were prepared by chemical conjugation and direct hybridization technique of hybridoma and hybridoma without screening markers. The specificity of BsAbs from culture supernatants or ascites was assayed by indirect ELISA and indirect immunoflurescence (IF). The results showed that BsAbs could specifically react with homologous serum IgM from patients with B CLL and cells carrying CD3 marker respectively. Cell combination test and LDH assay demonstrated that BsAb significantly increased the conjugate formation between lymphocyte activated kill (LAK) cells and Daudi cells, and enhanced the cytotoxic activity of LAK cells against Daudi cells.
文摘The expression vector of SmIg scFv fragment was constructed in patient with B cell chronic lymphocyte leukemia (B-CLL) and expressed in E. coli to obtain scFv fragment, and the effect of the protein on the proliferation of stimulated peripheral blood mononuclear cells (PBMC) was investigated in vitro. Two pairs of primers were designed, and variable region genes of light chain and heavy chain were amplified by PCR respectively from the pGEM-T vectors previously constructed in our laboratory which containing light chain gene or Fd fragment of heavy chain gene. The PCR product was digested, purified and inserted into pHEN2 vector to construct the soluble expression vector pHEN2-scFv. After the induction by IPTG, the scFv protein was identified by SDS- PAGE electrophoresis and purified by Ni-NTA-Chromatography. MTT was used to determine the effect of purified protein on the proliferation of stimulated PBMC in vitro. Plasmid PCR and restriction enzyme digestion of pHEN2-scFv revealed the pHEN2-scFv vector was constructed successfully. Id-scFv protein was expressed in positive clone after induced by IPTG. SDS-PAGE analysis showed that the relative molecular weight of fusion protein was about 30 kD (1 kD= 0. 9921 ku), which was consistent with the theoretically predicted value. Proliferation of PBMC could be induced by purified Id-scFv. It was suggested that the expression vector of SmIg scFv fragment was constructed successfully, and scFv protein was expressed and secreted from E. coil, which could induce proliferation of PBMC. This may lay an experimental foundation for further research of Id- HSP complex vaccine for B-CLL.
基金a grantfrom the NationalNature Science Foundation of China (Serial No.3 0 0 70 3 2 5 )Nature Science Foundation of Hubei Province
文摘Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2 % difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post GC cells.
文摘A double antibodies additivity ELISA test was employed to identify the epltopes which can be recognized by monoclonal antibodies (McAbs) against IgM from B chronic lymphocyte leukemia (B-CLL). The computer grouping programme analysis showed that 4 and- isotypic MaAbs could be divided into two groups and 10 anti- idiotype McAbs could be divided into four groups. The result was consistent with that of the indirect sandwich ELISA and inhibition ELISA test. It suggested that there were at least 6 distinct IgM epitopes which can react specifically with 14 McAbs. Our study indicated that the combination of the additivity ELISA test and the computer grouping programme analysis is of help in studying the relationship of the structure and function of antigen.
文摘End-stage kidney failure(ESKD)is a global issue where kidney replacement therapy imposes enormous economic burden to people of developing countries,in addition to the severe limitations to the availability of hemodialysis and peritoneal dialysis technique.The best option of kidney transplantation also requires lifelong combination immunosuppressive medicines,the cost of which is equally comparable to lifelong dialysis.A strategy of achieving transplant tolerance that requires minimum immunosuppressive medicines,although in experimental stage,also requires state-of-art technology with costly medicines and interventions.This is evidently beyond the reach of ESKD patients of developing countries.Hence,globally in developing countries,a need for an innovative but cost-effective tolerance protocol is a burning need for a successful transplant program.In brief,transplant tolerance is defined as a state of donorspecific unresponsiveness to the allograft antigens without the need for ongoing pharmacologic immunosuppression or with a minimal need.Current state-of-art techniques involves:(1)A state of hematological chimera,for complete tolerance;(2)Prope or partial tolerance where immune-reactive T-lymphocytes are inhibited using monoclonal antibodies;and(3)Chimeric antigen receptor for T-regulatory(T-reg)cell therapy using genetically engineered T-reg cells targeting specific Tlymphocyte receptors for inducing anergy.From our real-world experience in transplant management in post-transplant lympho-proliferative disorders(PTLD),we noticed frequently a drastic reduction in the need of immunosuppressive medicines following lympho-ablative therapy for PTLD.We recently published a case study on a real-world experience transplant case where we explained a partial or prope tolerance that developed after lymphocyte ablation therapy,following which the allograft was maintained with low dose dual standard immunosuppressive medicines.Based on this publication,we propose here an innovative tolerance protocol for living related low risk kidney transplantation for developing countries,in this opinion review.
文摘Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. JH-/- mice lack the JHgene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B iymphocytes in a number of immune responses; however, JH-/- mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and JH-/- mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of JH-/- mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the JH-/- animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exDosure in the pulmonary compartment.
文摘Interferon regulatory factor 4 (IRF4) and IRF8 are critical regulators of immune system development and function. In B lymphocytes, IRF4 and IRF8 have been shown to control important events during their development and maturation including pre-B cell differentiation, induction of B cell tolerance pathways, marginal zone B cell development, germinal center reaction and plasma cell differentiation. Mechanistically, IRF4 and IRF8 are found to function redundantly to control certain stages of B cell development, but in other stages, they function nonredundantly to play distinct roles in B cell biology. In line with their essential roles in B cell development, deregulated expressions of IRF4 and IRF8 have been associated to the pathogenesis of several B cell malignancies and diseases. Recent studies have elucidated diverse transcriptional networks regulated by IRF4 and IRF8 at distinct B cell developmental stages and related malignancies. In this review we will discuss the recent advances for the roles of IRF4 and IRF8 during B cell development and associated diseases.
基金supported by the grants from the National Key R&D Program of China(No.2020YFA0509200)the National Natural Science Foundation of China(Nos.82002622,81830081,31970718,and 81972203)+1 种基金the Shanghai Municipal Health Commission,Collaborative Innovation Cluster Project(No.2019CXJQ02)the Youth Project of Shanghai Municipal Health Commission(No.20194Y0096)
文摘Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.
基金supported by the National Natural Science Foundation of China for Xinhua Yin and Wenxiu Liu(81370319 and 81700318)the China Postdoctoral Science Foundation for Wenxiu Liu(2018M631957)+2 种基金the Hei Long Jiang Postdoctoral Fund for Wenxiu Liu(LBH-Z17145)Doctor Funds of the First Affi liated Hospital of Harbin Medical University for Wenxiu Liu(201613007)the Innovation and Entrepreneurship Training Program for College Students of Harbin Medical University for Wenxiu Liu(201910226157).
文摘Calcium-sensing receptor(CaSR),which was initially found in the parathyroid gland,is ubiquitously expressed and exerts specifi c functions in multiple cells,including immune cells.CaSR is functionally expressed on neutrophils,monocytes/macrophages,and T lymphocytes,but not B lymphocytes,and regulates cell functions,such as cytokine secretion,chemotaxis,phenotype switching,and ligand delivery.In these immune cells,CaSR is involved in the development of many diseases,such as sepsis,cryopyrin-associated periodic syndromes,rheumatism,myocardial infarction,diabetes,and peripheral artery disease.Since its discovery,it has been controversial whether CaSR is expressed and plays a role in immune cells.This article reviews current knowledge of the role of CaSR in immune cells.
文摘Blymphocyte stimulator (BLyS) is also known as B cell activating factor belonging to the tumor necrosis factor (TNF) family (BAFF), or TNF and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-I).^1-3 As a member of the TNF family, BLyS plays an important role in B cell development, and has been implicated in autoimmune diseases and B cell malignancies.
基金This work was supported partly by a grant from the National Natural Science Foundation of China to Dr. KONG Bei-hua (No. 30571953).Acknowledgement: We are grateful to Dr. GAO Wen-juan and Dr. LIU Jia for the technical support.
文摘Background BAFF, the B cell activation factor, is a member of the tumor necrosis factor (TNF) ligand family that binds to BCMA, TACI, and BAFF-R. Previous studies have shown that members of the TNF family are detected in human placental trophoblast cells, but the expression patterns of BAFF involved in human decidua and the differential expression of BAFF between normal pregnancy and miscarriage are still incompletely documented or unknown. This study was designed to investigate the expression of BAFF and BAFF-R in the trophoblast and decidua of normal early pregnant women and recurrent spontaneous abortion (RSA) patients.Methods Forty-five patients with RSA and 45 normal pregnant women were included in this study. By reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical experiments, we explored the expression of BAFF and BAFF-R in the maternal-fetal interface of normal early pregnant women and RSA patients.Results Analysis by RT-PCR and Western blotting revealed that BAFF was detected in both trophoblast and decidua of all the samples, and the expression level was higher in the tissues of normal early pregnant women (P〈0.05) than that of recurrent spontaneous abortion patients under the same gestational weeks. Messages for BAFF-R were absent. Immunohistochemical experiments showed that expression of BAFF was cell-specific which was localized to villous cytotrophoblast and syncytiotrophoblast cells in trophoblast and to stromal cells in decidua. Whereas BAFF was prominent on the trophoblast and decidua of normal early pregnant women, it was decreased in the tissues of RSA patients.Conclusions BAFF might steer maternal leukocytes away from a harmful immune response and toward a favorable one and play a potentially vital role for successful pregnancy.
文摘The prevalence of nasopharyngeal cancer (NPC) is high in the southern area of China and some other districts in the world. The pathogenesis of NPC is unclear. It is reported that some microRNAs (miR) are involved in the progression of NPC. This study aims to investigate the role of miR-21 in the induction of immune tolerance of NPC. In this study, NPC tissue was collected from patients with NPC. Assessment of miR was performed with real time quantitative RT-PCR. Western blotting was used to assess proteins of interleukin 10 and nuclear factor I-A (NFI-A), Immune ceils were analyzed by flow cytometry. The results showed that NPC cell line C666-1 and surgically removed NPC tissue expressed miR-21, which was upregulated by the presence of the Toll-like receptor 3 ligand, Poly h C. Exposure to miR-21 increased the expression of NFI-A and interleukin (IL)-IO in naive B cells. High frequency of IL-10+ B cells was detected in the NPC tissue. The NPC- or miR-21-primed B ceils suppressed cytotoxic CD8+ T cell activities. We conclude that NPC-derived miR-21 induces IL-10+ B ceils; the latter is capable of suppressing CD8+ T-cell activities, miR-21 may be a potential target in the treatment of NPC.