Regulatory T Cells and Their Molecular Markers in Peripheral Blood of the Patients with Systemic Lupus Erythematosus

CD4＋CD25＋ regulatory T cells （Tregs） and the expression of their molecular markers （GITR, Foxp3） in peripheral blood of the patients with systemic lupus erythematosus （SLE） were investigated in order to reveal the pathogenesis of SLE on the cellular and molecular levels. The level of Tregs in peripheral blood was detected by flow cytometry. The expression levels of GITR and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） were assayed by reverse transcriptase-polymerase chain reaction （RT-PCR）. The level of IL-6 in the plasma was measured by ELISA. Comparisons were made among 3 groups： the active SLE group, the inactive SLE group, and normal control group. The level of Tregs in the active SLE group and the inactive SLE group was significantly lower than in the normal control group （P〈0.01）. The level of Tregs in the active group was lower than in the inactive group with the difference being not significant （P〉0.05）. The level of Tregs in SLE patients was significantly negatively correlated with the disease active index in SLE （SLEDAI） （r=-0.81, P〈0.01）. The expression levels of GITR mRNA in PBMCs of the active SLE group and the inactive SLE group were significantly higher than in the normal control group （P〈0.05）, and those of Foxp3 mRNA in SLE patients of both active and inactive SLE groups were significantly lower than in the normal control group （P〈0.05）. There was no significant difference in the expression of GITR and Foxp3 mRNA between the active SLE group and inactive SLE group （P〉0.05）. The plasma levels of IL-6 in both the inactive SLE group and active SLE group were significantly higher than in the normal control group （P〈0.01）. The plasma level of IL-6 in the active SLE group was sig- nificantly increased as compared with that in the inactive SLE group （P〈0.05）, and the plasma level of IL-6 in SLE was significantly positively correlated with SLEDAI scores （r=0.58, P〈0.01） and significantly negatively correlated with the ratio of CD4＋CD25＋ cells/CD4＋ cells （r=-0.389, P〈0.05）. It was concluded that the levels of Tregs and Foxp3 mRNA in peripheral blood of SLE patients were decreased and the levels of GITR mRNA and plasma IL-6 were increased. The Tregs and their molecular markers GITR, Foxp3 as well as the plasma IL-6 might play an important role in the pathogenesis of SLE.

mRNA Expression of Chemokine Receptors on Peripheral Blood Mononuclear Cells and Correlation with Clinical Features in Systemic Lupus Erythematosus Patients

Objective To investigate the expressions of chemokine receptors and interleukin （IL） receptors on the peripheral blood mononuclear cells （PBMCs） from systemic lupus erythematosus （SLE） patients and their correlations with clinical features as well as SLE disease activity index （SLEDAI）. Methods The mRNA expressions of chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy controls were detected by reverse transcription-polymerase chain reaction, including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR5, CX3CR1, XCR1, IL-4R, and IL-10R. The clinical features of SLE patients were recorded. The correlations of chemokine receptors and IL receptors mRNA expressions with clinical features as well as SLEDAI were assayed using linear regression analysis. Results The level of CCR5 mRNA in SLE patients （including active and inactive SLE） was signifi- cantly higher than that in healthy controls （P〈0.05）, and there was no significant difference between active and inactive patients in this respect （P〉0.05）. CX3CR1 mRNA expression significantly increased from healthy control to inactive SLE to active SLE in sequence. The others （except for CCR8, CXCR3, and IL-1 OR） in active SLE patients weresignificantly higher than those in both inactive SLE patients and healthy controls （all P〈0.05）. There were positive correlations between SLEDAI and CCR2 （r=0.424, t=4.313, P〈0.001）, CCR3 （r=0.518, t=5.410, P〈0.001）, CCR4 （r=0.376, t=3.851, P〈0.001）, CCR6 （r=0.457, t=4.513,P〈0.001）, CXCR5 （r=0.455, t=4.629, P〈0.001）, CX3CR1 （r=0.44-5, t=4.523, P〈0.001）, as well as XCRI （r=0.540, t=5.445, P〈0.001）. And CCR5 mRNA expression level was positively correlated with IL-4R mRNA （r=0.313, t=2.353, P〈0.05）. The patients with myositis and cutaneous vasculitis simultaneously showed lower levels of CCR5 and CX3CRI, and CCR5 expression was negatively correlated with the scores of SLEDAI in SLE cases accompanied by photosensitivity （r=0.426, t=- 2.155, P〈0.05）. Conclusion Increased expressions of CCR5 and CX3CRI on PBMCs may be indicators in clinical survey for SLE.

Expression profiling of immune cells in systemic lupuserythematosus by single-cell RNA sequencing

Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains elusive.The advent of single-cell RNA sequencing(scRNA-seq)enables unbiased analysis of the molecular differences of cell populations at the single-cell level.We used scRNA-seq to profile the transcriptomes of peripheral blood mononuclear cells from an SLE patient compared with a healthy control(HC).A total of 16,021 cells were analyzed and partitioned into 12 distinct clusters.The marker genes of each cluster and the four major immune cell types(B cells,CD4+T cells,CD8+T cells,myeloid cells,and NK cells)were determined.Moreover,several genes involved in antigen processing and presentation through MHCII were highly enriched.GO enrichment analyses revealed abnormal gene expression patterns and signaling pathways in SLE.Of note,pseudotime analysis revealed that there was a different lineage hierarchy in the peripheral blood mononuclear cells(PBMCs)of the SLE patient,indicating that the cell states were substantially altered under disease conditions.Our analysis provides a comprehensive map of the cell types and states of the PBMCs of SLE patients at the single-cell level for a better understanding of the pathogenesis,diagnosis,and treatment of SLE.

Soluble MICB in Plasma and Urine Explains Population Expansions of NKG2D⁺CD4 T Cells Inpatients with Juvenile-Onset Systemic Lupus Erythematosus

Abnormal NKG2D ligand expression has been implicated in the initiation and maintenance of various auto-inflammatory disorders including systemic lupus erythematosus (SLE). This study’s goal was to identify the cellular contexts providing NKG2D ligands for stimulation of the immunosuppressive NKG2D+CD4 T cell subset that has been implicated in modulating juvenile-onset SLE disease activity. Although previous observations with NKG2D+CD4 T cells in healthy individuals pointed towards peripheral B cell and myeloid cell compartments as possible sites of enhanced NKG2DL presence, we found no evidence for a disease-associated increase of NKG2DL-positivity among juvenile-onset SLE B cells and monocytes. However, juvenile-onset SLE patient plasma and matched urine samples were positive by ELISA for the soluble form of the NKG2D ligands MICA and MICB, suggesting that kidney and/or peripheral blood may constitute the NKG2DL positive microenvironments driving NKG2D+CD4 T cell population expansions in this disease.

The Gene Expression Patterns of Peripheral Blood Mononuclear Cells in Patients with Systemic Lupus Erythematosus

This study examined the gene expression patterns of peripheral blood mononuclear cells （PBMCs） in patients with systemic lupus erythematosus （SLE） by using serial analysis of gene expression （SAGE） technology. Following the construction of serial analysis of gene expression （SAGE） library of PBMCs collected from 3 cases of familial SLE patients, a large scale of tag Sequencing was performed. The data extracted from sequencing files was analyzed with SAGE 2000 V 4.5 software. The top 30 expressed genes of SLE patients were uploaded to http：//david.niaid.nih.gov/david/ease.htm and the functional classification of genes was obtained. The differences among those expressed gene were analyzed by Chi-square tests. The results showed that a total of 1286 unique SAGE tags were identified from 1814 individual SAGE tags. Among the 1286 unique tags, 86.8% had single copy, and only 0.2% tags had more than 20 copies. And 68.4% of the tags matched known expressed sequences, 41.1% of which matched more than one known expressed sequence. About 31.6% of the tags had no match and could represent potentially novel genes. Approximately one third of the top 30 genes were ribosomal protein, and the rest were genes related to metabolism or with unknown functions. Eight tags were found to express differentially in SAGE library of SLE patients. This study draws a profile of gene expression patterns of PBMCs in patients with SLE. Comparison of SAGE database from PBMCs between normal individuals and SLE patients will help us to better understand the pathogenesis of SLE.

Peripheral CD4^(+)CD8^(+) double positive T cells:A potential marker to evaluate renal impairment susceptibility during systemic lupus erythematosus

Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.

Expression of c-kit receptor in peripheral blood mononuclear cells in patients with systemic lupus erythematosus

Objective： To determine the expression of c-kit receptor in peripheral blood mononuclear cells （PBMCs） in patients with systemic lupus erythematosus （SLE）, and analyze the relationship between the c-kit expression level of PBMCs and clinical parameters. Methods： Peripheral blood mononuclear cells in 47 patients with SLE and 21 healthy volunteers were collected. Expression of c-kit mRNA in PBMCs were determined with reverse transcription-polymerase chain reaction （RT-PCR）. The protein of c-kit receptor （CDllT） in PBMCs was measured by flow cytometry. Results： Expression of c-kit receptor protein and mRNA in patients with active or inactive SLE （ n = 47） were significantly higher than those in controls. The c-kit receptor of PBMCs in SLE patients were significantly higher than those in healthy controls （ n = 21 ）, the c-kit receptor of PBMCs in active patients （ n = 27） were significantly higher than those in inactive patients （ n = 20） and there was no significant difference was found between patients with inactive SLE and healthy controls（ P 〉 0.05）. The c-kit receptor of PBMCs in SLE have significant association with activity index. Conclusion： Production of c-kit receptor is aberrantly increased in PBMCs in patients with SLE. C-kit receptor might be more closely related to the clinical parameters in SLE patients, which might reflect the clinical status of SLE patients.

Ovarian function in patients with systemic lupus erythematosus:Pathogenesis,drug application and prospective therapies

Systemic lupus erythematosus(SLE)is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women.Currently,glucocorticoids and immunosuppressants are widely used to treat SLE patients.However,ovarian dysfunction occurs following the use of these drugs in women with SLE.Here,we summarize recent progress in terms of understanding ovarian injury,the effects of drug application and strategies to improve ovarian function in women with SLE.This review could be helpful to precisely cure SLE in women desiring to have offspring.

Serum IL-10 from systemic lupus erythematosus patients suppresses the differentiation and function of monocyte-derived dendritic cells

The role played by cytokines, other than interferon （IFN）-a, in the differentiation and function of dendritic cells （DCs） in systemic lupus erythematosus （SLE）, remains unclear. Serum interleukin-10 （IL-10） levels are generally elevated in SLE patients, which might modulate the differentiation of DCs. In this study, DCs were induced from monocytes either by transendothelial trafficking or by culture with granulocyte-macrophage colony-stimulating factor （GM-CSF） ＋ IL-4 ＋ tumor necrosis factor （TNF）-a. Both systems were used to investigate the effects of elevated serum IL-10 level on DC differentiation in SLE patients. The results showed that monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the expression of human leukocyte antigen （HLA）-DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited an impaired capacity to stimulate allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved in the pathogenesis of SLE by modulating the differentiation and function of DCs.

The Regulatory B Cell in Active Systemic Lupus Erythematosus Patients:A Systemic Review and Meta-analysis

Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory results.Therefore,we conducted a meta-analysis to verify the changes in Bregs in active SLE.Methods:We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed,Embase,Web of Science,Cochrane and CNKI.Due to the degree of heterogeneity is very high,we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls.Then,sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity.Results:Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis.The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls[0.259,(−1.150,1.668),p=0.719],with great heterogeneity(I2=97.5%).The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity,but after excluding the article conducted by Cai X and his colleagues,the percentages of Bregs were significantly higher in active SLE than those in controls[1.394,(0.114,2.675),p=0.033].The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score≥5,the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739),p=0.002],but when the threshold of SLEDAI score≥6 chosen for active SLE,the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759),p<0.001].Meanwhile,other subgroup analysis based on the different phenotypes of Bregs,diagnostic criteria,enrolled research countries,treatment status,and organ involvement did not differ in proportion of Bregs between SLE patients and controls.Conclusions:The study implies that Bregs may play a role in the pathogenesis of active SLE,and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.

Salvianolic acid A alleviates renal injury in systemic lupus erythematosus induced by pristane in BALB/c mice

OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Micewere then treated with daily oral doses of SAA for 5months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E)and periodic acid-Schiff(PAS)staining.Western blot analysis of renal tissue was also employed.RESULTS SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.CONCLUSION The results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.

Effects of Langchuangjing Granule (狼疮净冲剂) on Apoptotic of CD_4^+T and CD_(19)^+B in Spleen of BXSB Mice with Systemic Lupus Erythematosus

Objective: To study the effect on apoptosis of CD 4 +T、CD 19 +B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule (LCJG, and to probe into the mechanism of the tr eatment. Methods: The apoptosis was examined by the flow cytometric analysis and immunofluorescence double-staining method. Results: Apoptosis of male BXSB mice speeds up. LCJG can restrain the excessive apoptosis of CD 4 +T and CD 19 +B cells in spleen. Conclusion: LCJG treated systemic lupus erythematosus by restraining the excessive apoptosis of T, B lymphocytes, probably restraining the release of excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation of B cells and the produce of autoantibodies.

Oxidative stress as a potential causal factor for autoimmune hemolytic anemia and systemiclupuserythematosus

The kidneys and the blood system mutually exert infuence in maintaining homeostasis in the body. Because the kidneys control erythropoiesis by producing erythropoietinand by supporting hematopoiesis, anemia is associated with kidney diseases. Anemia is the most prevalent genetic disorder, and it is caused by a deficiency of glucose 6-phosphate dehydrogenase （G6PD）, for which sulfhydryl oxidation due to an insufficient supply of NADPH is a likely direct cause. Elevated reactive oxygen species （ROS） result in the sulfhydryl oxidation and hence are another potential cause for anemia. ROS are elevated in red blood cells （RBCs） under superoxide dismutase （SOD1） defciency in C57BL/6 mice. SOD1 defcient miceexhibit characteristics similar to autoimmune hemolytic anemia （AIHA） and systemic lupus erythematosus （SLE） at the gerontic stage. An examination of AIHA-prone New Zealand Black （NZB） mice, which have normal SOD1 and G6PD genes, indicated that ROS levels in RBCs are originally high and further elevated during aging. Transgenic overexpression of human SOD1 in erythroid cells effectively suppresses ROS elevation and ameliorates AIHA symptoms such as elevated anti-RBC antibodies and premature death in NZB mice. These results support the hypothesis that names oxidative stress as a risk factor for AIHA and other autoimmune diseases such as SLE. Herein we discuss the association between oxidative stress and SLE pathogenesis based mainly on the genetic and phenotypic characteristics of NZB and New Zealand white mice and provide insight into the mechanism of SLE pathogenesis.

Effect of Interferon-alpha in systemic lupus erthematosus (SLE) serum on the differentiation and maturation of dendritic cells derived from CD34^+ hematopoietic precursor cells

Objective： To study the effect of interferon-alpha IFN-α in the serum of SLE patients on the differentiation and maturation of dendritic cells （DCs） derived from CD34^＋ hematopoietic precursor cells （HPCs）. Methods： Serum samples from SLE patients and normal controls were collected and the concentration of IFN-α detected by ELISA. CD34^＋HPCs were purified from cord blood by a magnetic cell sorting system （MACS）, and cultured to differentiate to DCs. Normal serum, normal serum with exogenous IFN-α, SLE serum with raised levels of IFN-α, or SLE serum with anfi-IFN-α neutralizing antibody was added to the culture medium. The phenotype of DCs was analyzed by flow cytometry （FCM） and the capacity of DCs to stimulate allogenic T lymphocyte proliferation was evaluated in a mixed lymphocyte reaction by the Cell Counting Kit-8. Cytokine production was assessed by ELISA. Results： Serum levels of IFN-α were significantly higher in SLE patients than in normal controls and this correlated positively with disease activity. Cultured in SLE serum with raised levels of IFN-α, CD34^＋ HPCs could differentiate into DCs that expressed higher levels of HLA-DR, CD80 and CD86, and showed an enhanced allogenic T-cell stimulatory capacity, while producing lower levels of IL-12 and higher amounts of IL-10 compared with those DCs cultured in normal serum. Conclusion： Increased levels of IFN-α in SLE serum promotes the differentiation and maturation of DCs derived from CD34^＋ HPCs and could contribute to the pathogenesis of SLE.

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

Systemic lupus erythematosus(SLE)is characterized by a systemic dysfunction of both the innate and adaptive immune systems,leading to an attack on healthy tissues of the body.During the development of SLE,pathogenic features,such as the formation of autoantibodies against self-nuclear antigens,cause tissue damage including necrosis and fibrosis,with increased expression levels of the typeⅠinterferon-regulated genes.Standard treatments for lupus with immunosuppressants and glucocorticoids are not effective enough but cause side effects.As an alternative,more effective immunotherapies have been developed,including monoclonal and bispecific antibodies that target B cells,T cells,co-stimulatory molecules,cytokines or their receptors,and signaling molecules.Encouraging results have been observed in clinical trials with some of these therapies.Furthermore,a chimeric antigen receptor T cell therapy has emerged as the most effective,safe,and promising treatment option for SLE,as demonstrated by successful pilot studies.Additionally,some emerging evidence suggests that gut microbiota dysbiosis may significantly contribute to the severity of SLE,and the normalization of the gut microbiota through methods such as fecal microbiota transplantation presents new opportunities for effective treatment of SLE.

系统性红斑狼疮患者应用靶向B细胞治疗后发生中枢神经系统病变文献病例分析

目的探讨系统性红斑狼疮(SLE)患者经靶向B淋巴细胞生物制剂治疗后发生中枢神经系统不良反应的临床特征。方法检索国内外相关数据库(截至2023年5月),收集系统性红斑狼疮患者经贝利尤单抗、利妥昔单抗治疗后发生中枢神经系统病变的病例报告类文献,提取患者的基本信息、贝利尤单抗或利妥昔单抗用药情况(用法用量、单用或联用、联用方案等)、中枢神经系统病变发生时间、临床表现、影像学特征、临床治疗及转归等,并进行描述统计分析。结果检索到进行性多灶性脑白质病(PML)患者14例,发病年龄(50.71±11.45)岁;可逆性后部脑病综合征(PRES)患者24例,发病年龄(30.67±14.93)岁。纳入有详细病例报道的患者共7例,7例患者均未合并HIV感染、恶性肿瘤及其他自身免疫性疾病。7例患者均经磁共振检查确诊,均未行脑组织活检。临床表现:癫痫5例,视物模糊或视力丧失3例,构音障碍或失语2例,头痛2例,昏迷1例,血压升高4例。最终7例患者中1例死亡。结论应用靶向B细胞治疗后,SLE患者中枢神经系统副作用多发生在疾病活动期且合并使用其他免疫抑制剂时。患者的临床表现容易与神经精神狼疮混淆,导致病情延误,提示在使用靶向B细胞生物制剂治疗时,应评估SLE患者发生中枢神经系统副作用的潜在风险。

TNFAIP3表达水平对MRL/lpr小鼠B淋巴细胞功能及其炎症反应的影响

目的探讨肿瘤坏死因子α诱导蛋白3(TNFAIP3)对MRL/lpr小鼠B淋巴细胞功能的影响,进一步探索其在免疫及炎症反应中发挥功能的具体作用机制,为系统性红斑狼疮(SLE)的临床研究提供实验依据。方法采用腺相关病毒(AAV)感染提高MRL/lpr小鼠TNFAIP3的表达,RT-qPCR及Western blot检测B淋巴细胞中TNFAIP3、Toll样受体7(TLR7)、Toll样受体9(TLR9)基因及蛋白表达水平,ELISA法检测血清抗ds-DNA抗体、TNF-α和IL-6的水平,分析TNFAIP3与TLR7/TLR9之间的关系。结果成功过表达MRL/lpr小鼠B淋巴细胞的TNFAIP3后,该组小鼠血清中抗ds-DNA抗体、TNF-α和IL-6的水平与对照组相比明显降低(P<0.05)。Western blot及RT-qPCR检测显示TLR7、TLR9蛋白及mRNA水平与对照组相比明显降低(P<0.05)。结论TNFAIP3可能通过抑制B淋巴细胞中TLR7/TLR9蛋白及mRNA表达水平,抑制MRL/lpr小鼠体内自身抗体和炎症因子的产生,从而缓解MRL/lpr小鼠的病情进展。

Increased serum IL-10 in lupus patients promotes apoptosis of T cell subsets via the caspase 8 pathway initiated by Fas signaling

We sought to investigate the expression of Fas and FasL on T cell surface and caspase 8 involvement in T cell apoptosis promoted by serum IL-10 in systemic lupus erythematosus （SLE） patients. Cells and sera were obtained from 35 SLE patients. Apoptosis of T cells in patients with SLE was increased and associated with the SLE disease activity index （SLEDAI）. Elevated expression of Fas and FasL on T cell surface contributed to increased apoptosis of T cells. Increased IL-10 in the sera of SLE patients was capable of inducing Fas and FasL expression on CD4^＋T cell surface, promoting apoptosis of this cell subset. Decreased IL-10 serum levels and low expression of Fas were found in 5 patients of the first follow-up group after 2-month treatment. In another group with one-year treatment, the SLEDAI declined to inactive scores. Serum IL-10 was decreased significantly, and expression of Fas and FasL on T cells was also reduced. Declined apoptosis was predominant only in CD4^＋T cell subset. When sera with high level of IL-10 were used to culture PBMCs from healthy controls, activated caspase 8 was elevated in CD3^＋T, CD4^＋T and CD8^＋T cells. The study showed that serum IL-10 induced apoptosis of T cell subsets via the caspase 8 pathway initiated by Fas signaling. Increased apoptosis of T cells contributes to autoantigen burden, which is pathogenic in the development of SLE.

miR-125b-5p修饰脐带间充质干细胞对系统性红斑狼疮的免疫调控机制

目的:研究miR-125b-5p修饰脐带间充质干细胞(umbilical cord mesenchymal stem cells, UC-MSCs)对系统性红斑狼疮(systemic lupus erythematosus, SLE)的免疫调控作用机制。方法:实时荧光定量PCR检测miR-125b-5p在UC-MSCs和SLE患者、健康体检者外周血单个核细胞中的表达水平;Annexin V-FITC/PI凋亡检测试剂盒检测miR-125b-5p对UC-MSCs的凋亡影响;每周对MRL/lpr小鼠进行尾静脉注射UC-MSCs, 5周后流式细胞术检测各组小鼠脾细胞T淋巴细胞亚群分化情况;ELISA法检测各组MRL/lpr小鼠血清中白细胞介素(interleukin, IL)-4和IL-17A表达水平;苏木精-伊红染色法观察MRL/lpr小鼠肺和肾组织病理变化。结果:与健康对照组相比,SLE患者外周血单个核细胞中miR-125b-5p的表达水平显著下调(P<0.01);与UC-MSCs相比,miR-125b-5p转染UC-MSCs组miR-125b-5p的表达水平显著上调(P<0.01)。miR-125b-5p转染UC-MSCs 48 h可显著提高细胞存活率(P<0.01);与未处理的MRL/lpr小鼠组相比,miR-125b-5p修饰UC-MSCs对MRL/lpr小鼠脾脏Th17细胞分化具有明显的下调作用(P<0.05),且在小鼠血清中IL-4表达水平明显升高(P<0.05),IL-17A表达水平明显减低(P<0.05)。经miR-125b-5p修饰的UC-MSCs治疗后,MRL/lpr小鼠肺和肾组织内炎性细胞浸润和微血栓减少。结论:miR-125b-5p修饰UC-MSCs对SLE具有免疫调控作用。