Huoxue Tongjiang decoction-resisted reflux esophagitis by activation stem cell factor/c-kit/interstitial cell of cajal pathway and regulating the T-helper 17/regulatory T-cells balance in rats

Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.

非小细胞肺癌不同胸腔积液严重程度及预后患者lncRNA MEG3表达及其与Th17/CD4^(+)T细胞的关系

目的:研究非小细胞肺癌(NSCLC)不同胸腔积液严重程度及预后患者lncRNA MEG3表达及其与Th17/CD4^(+)T细胞的关系。方法:选取2020年1月至2022年12月福建医科大学附属泉州第一医院收治的104例NSCLC恶性胸腔积液患者作为研究对象,根据胸腔积液量分为3组:少量胸腔积液组(35例)、中量胸腔积液组(42例)、大量胸腔积液组(27例)。根据患者疾病实际发展转归分为预后良好组(29例未出现复发和转移)和预后不良组(75例出现复发和转移)。另选取同期于福建医科大学附属泉州第一医院治疗的60例肺炎良性胸腔积液患者作为对照组。实时荧光定量PCR检测两组胸腔积液中MEG3表达。收集受试者外周静脉血,流式细胞术检测外周血Th17细胞、CD4^(+)T细胞比例,并计算Th17/CD4^(+)T。对比各组患者lncRNA MEG3及外周血Th17、CD4^(+)T细胞水平。Logistic回归分析NSCLC胸腔积液及预后的影响因素。结果:NSCLC组胸腔积液lncRNA MEG3表达及CD4^(+)T细胞百分比低于对照组,Th17细胞百分比、Th17/CD4^(+)T高于对照组(P<0.05)。大量胸腔积液组lncRNA MEG3表达及CD4^(+)T细胞百分比低于少量胸腔积液组、中量胸腔积液组,中量胸腔积液组lncRNA MEG3表达及CD4^(+)T细胞百分比低于少量胸腔积液组,大量胸腔积液组Th17细胞百分比、Th17/CD4^(+)T高于少量胸腔积液组、中量胸腔积液组,中量胸腔积液组Th17细胞百分比、Th17/CD4^(+)T高于少量胸腔积液组(P<0.05)。预后不良组lncRNA MEG3表达及CD4^(+)T百分比低于预后良好组,而Th17细胞百分比、Th17/CD4^(+)T高于预后良好组(P<0.05)。Logistic回归分析结果显示,lncRNA MEG3为NSCLC胸腔积液的保护因素,Th17/CD4^(+)T为危险因素(P<0.05);lncRNA MEG3为NSCLC预后的保护因素,Th17/CD4^(+)T为危险因素(P<0.05)。结论:NSCLC不同胸腔积液严重程度及预后患者lncRNA MEG3表达及Th17/CD4^(+)T不同,且lncRNA MEG3为NSCLC胸腔积液及预后的保护因素,Th17/CD4^(+)T为危险因素,可作为胸腔积液严重程度及预后诊断的有效生物标志物。

Modulating the crosstalk between macrophage and Th17: potential mechanism of natural products on acute lung injury

Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.

Detection and Clinical Significance of Th17/Treg Cell-Related Factors in Patients with Gestational Diabetes Mellitus

Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method was used to collect the clinical data of 42 patients who were hospitalized in the Affiliated Hospital of Hebei University and received the diagnosis of GDM from January 2018 to December 2022,as well as 42 patients with normal pregnancies during the same period.The Th17/Treg expression levels and metabolism-related indexes in the peripheral blood of patients were detected by radioimmunoassay.Results:The relative expression of Th17 in the serum of patients in the GDM group was significantly higher than that of the control group,and the level of Treg was significantly lower than that of the control group(P<0.05);the levels of FBG,FINS,2hBG,TC,TG and HOMA-IR of the patients in the GDM group were significantly higher than that of the control group,and the level of HOMA-βwas significantly lower than that of the control group(P<0.05).Conclusion:The imbalance of the Th17/Treg cell ratio in patients with GDM may be related to their disease progression and prognosis,providing new ideas and strategies for the clinical treatment of GDM.

Anti-inflammatory effect of miR-125a-5p on experimental optic neuritis by promoting the differentiation of Treg cells

Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodulatory effects on autoimmune diseases.However,it remains unclear whether miR-125 a-5 p has effects on optic neuritis.In this study,we used adeno-associated virus to overexpress or silence miR-125 a-5 p in mice.We found that silencing miR-125 a-5 p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve.Ove rexpression of miR-125 a-5 p suppressed inflammation of the optic nerve,protected retinal ganglion cells,and increased the percentage of Treg cells.Our findings show that miR-125 a-5 p exhibits anti-inflammatory effects through promoting the diffe rentiation of Treg cells.

Potential role of Th17 cells in the pathogenesis of inflammatory bowel disease

The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.

Decidual stromal cells recruit Th 17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

T helper 17 （Th17） cells have both regulatory and protective roles in physiological conditions. The Th17 subset and the cytokine interleukin-17A （IL-17A） have been implicated in the pathogenesis of certain autoimmune diseases, several types of cancer and allograft rejection. However, the role of Th17 cells at the maternal/fetal interface remains unknown. Here, we demonstrate that Th17 cells are present in decidua and are increased in the peripheral blood of 10 clinically normal pregnancies based on intracellular cytokine analysis. Our results suggest a potential role of Th17 cells in sustaining pregnancy in humans. Furthermore, we demonstrate that decidual stromal cells （DSCs） but not trophoblast cells recruit peripheral Th17 cells into the decidua by secreting CCL2. The recruited Th17 cells promote proliferation and invasion and inhibit the apoptosis of human trophoblast cells by secreting IL-17 during the first trimester of pregnancy. These findings indicate a novel role for Th17 cells in controlling the maternal-fetal relationship and placenta development.

Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients

BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+ IL-17+ cells were measured by flow cytometry The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+ IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56±0.43% versus 1.79±0.44% P<0.001). The frequency of CD4+ IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002).CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.

YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Mechanism of Liancao-Xieli capsule in the treatment of ulcerative colitis through the differentiation of Th17 and Treg cells

Objective:To observe the effect of Liancao-Xieli Capsule on STAT signal pathway and T cell differentiation in mouse model of ulcerative colitis;Methods:Forty BALB/c mice were randomly divided into the control group,model group,mesalazine group and Liancao-Xieli capsule group.Except the control group,the other three groups were treated with 3%dextran sodium sulfate free drinking water to construct the model of ulcerative colitis.During the modeling period,each group was given corresponding drugs for intervention,while the control group and the model group were given the same volume of distilled water by gavage as the control.After treatment,HE staining was used to observe the pathological changes of colon tissue,flow cytometry was used to detect the proportion of Th17 and Treg cells in spleen and mesenteric lymph nodes,and ELISA was used to detect TGF-β,IL-6 and IL-17A in colon tissue.Western blot was used to detect the expression levels of related proteins in STAT3/ROR-γt and STAT5/Foxp3 signaling pathways.Results:Compared with the model group,the body weight,colon length and the content of TGF-βin the colon tissue of the mice in the Liancao-Xieli capsule group increased significantly after the experiment,while the DAI score,colon histopathology score,and the contents of IL-6 and IL-17A in the colon tissue were significantly reduced,and the difference was statistically significant(P<0.01).At the same time,Liancao-Xieli capsule can reduce the ratio of Th17 cells and the ratio of Th17/Treg in the spleen and mesenteric lymph node tissues of UC mice,and increase the ratio of Treg cells,and the difference is statistically significant when compared with the model group(P<0.01).In addition,compared with the model group,the expression levels of p-STAT3 and RORγt protein in the colon tissue of the Liancao-Xieli capsule group were significantly reduced,and the expression levels of p-STAT5 and Foxp3 protein were significantly increased after treatment,and the differences are statistically significant(P<0.01),while the expression levels of STAT3 and STAT5 proteins in colon tissue did not change significantly,and the difference was not statistically significant(P>0.05);Conclusion:Liancao-Xieli Capsule can regulate the immune balance of Treg/Th17 and improve the intestinal inflammation of UC.Its mechanism of action is mainly through inhibiting STAT3/ROR-γt and promoting the activation of STAT5/Foxp3 signaling pathway.

Silencing of <i>ERK2</i>with Small Interference RNA Regulates the Expression of CXCL1 in Th17 Cell

Patients with steroid-resistant asthma had their monocyte-derived TH17 cells collected. The expression levels of ERK2 in the TH17 were silenced and inhibited using ERK2 specific small interfering RNA (siRNA). By screening of CXCL1 and IL-17A in the TH17 culture supernatant, the expression levels of ERK2 and CXCL1 were determined. Using targeted siRNA to inhibit ERK2, the expression of ERK2 in the TH17 was reduced. Furthermore, inhibiting ERK2 hindered CXCL1 expression and decreased CXCL1 and IL-17A production. These findings suggest that ERK2 is involved in the synthesis of CXCL1 and IL-17A, two proteins that play a key role in the pathogenesis of hormone-resistant asthma.

Th17 Cells and Tregs in HTLV-1 Infection

HTLV-1(human T-lymphotropic virus type 1)causes chronic infection ofhuman T lymphocytes.HTLV-1 infection is known to be related to multiple diseases,including neoplastic growth of HTLV-1-infected T cells(ATL)and neoplastic inflammatory conditions,such as HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP),Sjogren's syndrome with arthritis,polymyositis uveitis,and bronchoalveolitis.Regulatory T cells(Tregs)regulate inflammatory cells,such as Th17 cells.The purpose of this study was to evaluate Tregs and Th17 cells,as well as the expression of related transcription factors(ROR-γ1 and FOXP3)and cytokines(IL-10,TGF-β,IL-6,and IL-17A)in HTLV-1 infection.

Th17细胞与CD4^+CD25^+调节性T细胞在儿童过敏性紫癜发病机制中的作用

目的探讨Th17细胞与CD4+CD25+调节性T细胞在儿童过敏性紫癜(HSP)免疫发病机制中的作用。方法过敏性紫癜急性期患儿48例,采用流式细胞术检测外周血CD4+CD25+调节性T细胞(CD4+CD25+Treg)的比例,采用荧光定量PCR(real-time PCR)检测CD4+ T细胞IL-17A、IL-17F、转录因子ROR-γt、Foxp3及细胞因子IL-6、TGF-β等mRNA表达;同期40例同龄健康儿童作为对照。结果过敏性紫癜急性期患儿CD4+ T细胞高表达IL-17A及IL-17F(P<0.01)。Th17细胞转录因子ROR-γt及前炎症细胞因子IL-6 mRNA表达明显增高(P<0.01)。CD4+CD25+调节性T细胞比例明显低于正常对照组(P<0.01),其转录因子Foxp3表达亦明显降低(P<0.01)。结论Th17等促炎性T细胞高表达和CD4+CD25+调节性T细胞数量减少导致的免疫抑制效应不足,是导致过敏性紫癜免疫失衡的重要原因,IL-6高表达与此密切相关。

急性哮喘患者外周血中Th17细胞的变化及其意义

目的:探讨哮喘急性发作期患者外周血中Th17细胞的变化及其与哮喘严重程度的关系。方法:选取轻度急性哮喘患者、重度急性哮喘患者和健康对照者各10名。从血清单个核细胞中分离T淋巴细胞,流式细胞仪检测阳性Th17细胞率,分析其与哮喘严重程度的关系。结果:轻度急性哮喘组和重度急性哮喘组外周血阳性Th17细胞均较健康对照组增高(P<0.05),而重度哮喘组高于轻度哮喘组(P<0.05)。重度哮喘组外周血IL-17水平明显高于轻度哮喘组和健康对照组(P<0.05)。外周血中Th17阳性细胞数与急性哮喘严重程度呈正相关(r=0.869,P<0.05)。结论:急性哮喘患者外周血Th17细胞表达增加,且与其病情的严重程度呈正相关。

沙利度胺联合环孢素A及泼尼松治疗中低危骨髓增生异常综合征疗效及对Th17和Th22细胞水平的影响

目的应用沙利度胺联合环孢素A及泼尼松(TCP方案)治疗中低危骨髓增生异常综合征(MDS),观察临床疗效,并探讨TCP方案对Th17、Th22细胞水平的影响。方法 2009年6月-2013年9月兰州大学第二医院血液科收治的62例中低危MDS患者分为2组,A组(35例)接受TCP方案,B组(27例)单用环孢素A,评估TCP方案治疗的有效性。应用流式细胞技术检测治疗前后Th17、Th22细胞表达水平的变化,酶联免疫吸附实验检测细胞因子IL-17、IL-22、IFN-γ、IL-10。结果 A组有效23例(65.71%),高于B组(44.44%),两组比较差异有统计学意义(P<0.05)。对A组的23例和B组的13例进行了Th17和Th22细胞表达水平观察,与健康对照组比较,治疗前两组Th17和Th22细胞比例均有不同程度升高,P<0.05。与治疗前比较,两组Th17细胞在治疗后均减低(P<0.05),A组Th22细胞在治疗后减低(P<0.05),B组Th22细胞在治疗后差异无统计学意义(P>0.05)。两组治疗前IL-17、IL-22水平与健康对照组比较差异无统计学意义(P>0.05),治疗后IL-17、IL-22水平也无明显变化(P>0.05)。两组IFN-γ水平均较治疗前降低(P<0.05);A组IL-10水平在治疗后升高(P<0.05)。两组患者均未出现3、4级血液学毒性。A组9例和B组4例患者出现肝功能异常,A组1例患者出现肾功能异常,所有肝、肾功能异常者经停药或对症治疗后均好转。结论 TCP方案是治疗MDS的有效组合方案,联合检测Th17和Th22将有助于指导免疫调节剂的使用。

Th17细胞在结核性胸膜炎患者外周血及胸水中的表达以及诊断意义

目的探讨Th17细胞在结核性胸膜炎中的作用。方法收集住院收治的初治结核性胸膜炎患者30例和非结核性胸膜炎患者20例,另选择健康体检人员20例为正常对照组。在入院时和治疗后分别抽取外周血和胸水,并使用流式细胞术检测外周血及胸水中Th17细胞比例的变化。结果我们发现在Th17细胞在结核性胸膜炎患者中出现了显著性的上升,而非结核性胸膜炎患者虽然也出现了一定量的升高,但和结核性胸膜炎患者相比,还是存在显著性的差异。此外,我们又检测了经过治疗的结核性胸膜炎患者的Th17细胞比例,发现经过治疗之后,不论外周血还是胸水中,Th17细胞的比例均有显著性的下降。结论上述结果说明Th17细胞可能全程参与到了结核性胸膜炎的发病过程中,并且可能成为其诊断的重要依据。

CCR6-CCL20趋化轴在TH17细胞介导的肺纤维化大鼠肺组织中作用机制的研究

目的探讨CCR6-CCL20趋化轴在Th17细胞介导的肺纤维化大鼠肺组织中作用。方法随机将63只雄SD大鼠为:N组(生理盐水对照组)、B组(肺纤维化模型组)、D组(地塞米松治疗组),采用经气管内注入博来霉素致大鼠肺纤维化模型,对各组大鼠肺组织,分别采用HE染色观察病理变化;流式细胞术计数Th17细胞;免疫组化法评价CCR6表达;酶联免疫吸附试检测CCL20水平;结果 TH17细胞、CCR6、CCL20、在B、D组大鼠肺组织中不同时间点与N组相比较表达均明显增高(P<0.05),以造模7 d最为显著。TH17细胞计数水平与CCR6、CCL20表达有显著的相关性(Th17 vs.CCR6,r=0.693,P<0.01;Th17 vs CCL20,r=0.761,P<0.01)。结论 Th17细胞介导大鼠肺组织纤维化过程中,CCR6-CCL20起到重要的趋化Th17细胞作用。

Th-17细胞因子在哮喘期可促进中性粒细胞产生白细胞介素17A和17F

背景:在重度哮喘患者中,Th-17细胞及其衍生的细胞因子(白细胞介素17,白细胞介素21,白细胞介素22)表达升高,但具体的调节机制尚未明确。目的:探讨重症哮喘患者Th-17调节性细胞因子对中性粒细胞中的白细胞介素17的影响。方法:纳入哮喘患者28例,正常健康受试者28名。用白细胞介素21、白细胞介素23和白细胞介素6细胞因子刺激从2组受试者外周血分离的中性粒细胞,并测定它们产生白细胞介素17A和白细胞介素17F的能力。使用流式细胞仪测量刺激后中性粒细胞中的信号转导和转录激活因子3(STAT3)磷酸化水平。通过使用特定化学抑制剂阻断转录激活因子3磷酸化来判断白细胞介素17基因表达是否与其有关。研究由桂林医学院附属医院的伦理委员会审查和批准,伦理审批号:院字2017第013号。结果与结论:①相对于健康对照组,用白细胞介素21、白细胞介素23和白细胞介素6刺激哮喘患者的中性粒细胞,能够显著提高白细胞介素17A和白细胞介素17F的产生;②使用白细胞介素21、白细胞介素23和白细胞介素6细胞因子刺激中性粒细胞均能够增强转录激活因子3磷酸化;③同时,使用特异性化学抑制剂抑制转录激活因子3的磷酸化能够显著阻断中性粒细胞产生白细胞介素17的能力,这表明转录激活因子3激活可能是介导白细胞介素17基因表达的主要路径;④结果说明,严重哮喘患者肺部的中性粒细胞浸润可能是促炎性细胞因子白细胞介素17A和白细胞介素17F的重要来源,转录激活因子3途径可能是严重哮喘期间调节中性粒细胞的潜在靶点。