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.

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.

牙周基础治疗对牙周炎伴2型糖尿病患者Treg/Th17细胞平衡及相关细胞因子表达水平的影响

目的探讨牙周基础治疗对牙周炎伴2型糖尿病患者Treg/Th17细胞比例及相关细胞因子表达水平的影响。方法选取2021年1月至2022年6月本院口腔门诊收治的牙周炎伴T2DM患者80例作为研究对象,随机分为A组和B组,每组40例。A组接受牙周基础治疗,B组仅进行口腔卫生宣教。两组患者均接受常规血糖调控治疗。检测比较两组在治疗前、后3个月的牙周临床指数,糖、脂代谢指标,外周血Th17/Treg细胞及血清相关细胞因子表达。结果治疗后3个月,B组患者的牙周状况指标与治疗前相似,而A组患者的牙周状况指标(PI,BI,PD)出现显著下降趋势(P<0.05)。B组患者血清TG、HDL-C、LDL-C、FBG、HbAlc、FINS、HOMA-IR表达水平与治疗前相似,而A组患者血清FBG、TG、HbAlc、FINS、HOMA-IR表达水平明显低于治疗前和B组水平,HDL-C表达水平则明显高于治疗前和B组水平,差异有统计学意义(P<0.05)。治疗后3个月,A组患者外周血Th17细胞的比例明显下降,Treg细胞比例明显增高,但B组变化不明显,与A组比较,差异具有统计学意义(P<0.05)。治疗后3个月,两组患者血清中TNF-α、IL-17、IL-6表达均呈现下降趋势,A组下降幅度更显著(P<0.05)。结论对T2DM伴牙周炎患者进行牙周基础治疗干预,不仅能明显改善患者糖脂代谢和降低胰岛素抵抗程度,同时能调节Th17/Treg失衡,降低血清中相关炎性因子。

川芎-独活-牛膝配伍在骨关节炎发病中TH17/Treg细胞免疫平衡的调节作用

目的:探讨川芎-独活-牛膝配伍在骨关节炎发病中Th17/Treg细胞免疫平衡的调节作用。方法:购置SPF级无菌C57BL/6小鼠40只,随机取小鼠10只为空白对照组;剩余30只小鼠采用Hulth-Telhag方法构建膝关节炎动物模型,并随机分为模型组、异戊酸组和川芎-独活-牛膝配伍组,各10只。空白对照组和模型组腹腔灌注等体积生理盐水,异戊酸组腹腔灌胃异戊酸,川芎-独活-牛膝配伍组采用川芎-独活-牛膝水煎液灌胃,各组均持续7d干预,比较各组HE染色结果、炎性因子水平及Th17/Treg细胞免疫。结果:HE染色下异戊酸组伴有轻度关节软骨破坏,可见少许炎症细胞浸润;川芎-独活-牛膝配伍组关节软骨破坏不明显,炎症细胞亦相对较少;川芎-独活-牛膝配伍组IL-17、IL-6、IL-4低于异戊酸组(P<0.05);IL-10和TGF高于异戊酸组(P<0.05);流式细胞仪测定结果表明:川芎-独活-牛膝配伍组干预7d后Th17细胞低于异戊酸组和模型组(P<0.05);Treg细胞高于异戊酸组和模型组(P<0.05)。结论:川芎-独活-牛膝配伍用于骨关节炎中能减轻膝关节滑膜及软组织损伤,降低体内炎性因子水平,其机制可能与Th17/Treg细胞免疫平衡的调节有关。

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.

Effects of early enteral nutrition on Th17/Treg cells and IL-23/IL-17 in septic patients

BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P <0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728). CONCLUSION EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL- 23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.

Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients

AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10(1.05-4.60) pg/m L vs 0.00 pg/m L, P < 0.001], TGF-β1(19.94 ± 3.35 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.02), IL-10(2.83 ± 0.44 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.008), and IL-17 A [6.30(2.50-15.60) pg/m L vs 0(0.00-0.05) pg/m L, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-β, IL-6 and IL-17 A in the lc SSc subset vs control subjects, as it follows: IL-10(3.32 ± 0.59 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.003), TGF-β1(22.82 ± 4.99 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.031), IL-6 [2.08(1.51-4.69) pg/m L vs 0.00 pg/m L, P < 0.001], and IL-17 A [14.50(8.55-41.65) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001]. Furthermore, circulating IL-17 A was higher in lc SSc as opposed to dc SSc subset(31.99 ± 13.29 pg/m L vs 7.14 ± 3.01 pg/m L, P = 0.008). Within the dc SSc subset, raised levels of IL-17 A and IL-6 were detected vs healthy controls: IL-17 A [2.60(0.45-9.80) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001], IL-6 [2.80(1.03-7.23) pg/m L vs 0.00 pg/m L, P < 0.001]. Regarding the stages of the disease, TGF-β1 serum levels were increased in early stage against late stage, independently from the SSc phenotype(30.03 ± 4.59 ng/m L vs 13.08 ± 4.50 ng/m L, P = 0.017).CONCLUSION It is likely that the altered percentage of Th17 and CD4+CD25-Fox P3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease.

Correlation between microRNA-21 and expression of Th17 and Treg cells in microenvironment of rats with hepatocellular carcinoma

Objective: To study the correlation between mi R-21 and Treg/Th17 ratio in the microenvironment of rats with hepatocellular carcinoma. Methods: Diethylnitrosamine was used to build the hepatocel ular carcinoma model of rats; the content of Treg cells and Th17 cells and the expression of mi R-21 in the peripheral blood of rats with hepatocellular carcinoma were detected. The statistical analysis was performed on the correlation between mi R-21 expression and Treg/Th17 ratio. Results: Hepatocellular carcinoma model of rats was successfully constructed. The proportion of Th17 cells among all CD4+T cells in the peripheral blood of rats with hepatocellular carcinoma was 5.319%, which was higher than the control group; while the proportion of Treg cells was 9.472%, which was higher than the control group. Treg/Th17 ratio in the model group was 1.781, compared with 1.478 in the control group. The expression of mi R-21 was increased in the peripheral blood of rats with hepatocellular carcinoma and it showed a positive correlation with the ratio of Treg/Th17. Conclusions: There is a positive correlation between the expression level of miR-21 and the ratio of Treg/Th17.

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.

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.

不同病因肝衰竭患者外周血单个核细胞HLA-DR基因水平及血Th17和CD4^+CD25^+Treg细胞百分比的变化

目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;慢性乙型肝炎患者17例和正常人10例。采用PCR法检测PBMCs中HLA-DR m RNA水平,使用流式细胞仪检测CD4^+CD25^+Treg和Th17细胞百分比。结果乙型肝炎肝衰竭患者HLA-DR m RNA水平为(134.5±15.2),显著高于药物性肝损伤组的(17.9±1.2)、酒精性肝病组的(19.6±2.0)和自身免疫性肝炎组的[(11.2±1.2),P<0.05];不同病因肝衰竭患者Th17和CD4^+CD25^+Treg细胞百分比[分别为(4.4±0.6)%和(3.9±0.6)%左右]的差异无统计学意义(P>0.05),但与慢性乙型肝炎[分别为(3.7±0.2)%和(6.1±0.4)%和正常人(2.1±0.7)%和(7.0±0.9)%比,均有显著性差异(P<0.05);对不同病因肝衰竭患者进行动态观察发现,19例死亡患者CD4^+CD25^+Treg细胞百分比呈持续下降,直至死亡,而31例生存患者则逐渐恢复至接近正常水平。结论外周血单个核细胞HLA-DR m RNA水平及Th17和CD4^+CD25^+Treg细胞百分比的变化与肝衰竭患者的病情密切相关,可作为判断肝衰竭严重程度及预后的指标。

Runx3对寻常性银屑病患者Th17/Treg细胞分化的影响及其作用机制

目的探讨Runx3对银屑病患者Th17,Treg细胞分化的影响及作用机制。方法收集58例银屑病患者和50例健康对照者血液样本,应用密度梯度离心法分离外周血CD4^+T细胞,qRT-PCR检测Runx3的mRNA水平;采用RNA干扰法下调Runx3的表达水平,流式细胞仪检测Th17和Treg细胞水平;ELISA法测定外周血IL-17,IL-23,TGF-β,IL-10含量;实时定量PCR法检测RORγt,Foxp3的mRNA水平。结果与对照组相比,银屑病患者外周血CD4^+T细胞中Runx3的表达明显升高。Runx3-siRNA转染后,Th17/Treg细胞比值降低,同时伴随有Th17型炎性因子IL-17,IL-23表达下降以及Treg型抗炎因子TGF-β,IL-10的上调。机制分析证实,Runx3沉默后,细胞中Th17转录因子RORγt明显下降,而Treg转录调节因子Foxp3水平增加。结论 Runx3可通过RORγt,Foxp3调控CD4^+T细胞向Th17,Treg型细胞的分化,影响银屑病患者Th17/Treg比例的失衡,提示其可作为银屑病防治的新方向。

Treg细胞、Th_(17)细胞及mTOR信号通路与狼疮性肾炎发病机制的研究进展

狼疮性肾炎(LN)是系统性红斑狼疮(SLE)患者最严重的并发症和死亡的主要原因之一。狼疮性肾炎自身免疫机制研究较多,近年来,Treg细胞、Th17细胞及m TOR信号通路在LN发病机制中研究更加深入。本文就Treg细胞(CD_4^+Treg细胞,CD_4^-CD_8^-T细胞,CD_8^+Treg细胞)、Th_(17)细胞及mTOR信号通路与LN的发病机制作一综述。

MMP-3/TIMP-1、Th17/Treg在类风湿关节炎中的作用及其临床意义

多种研究表明,基质金属蛋白酶-3(matrix metalloproteinase,MMP-3)的高表达在类风湿关节炎(rheumatoid arthritis,RA)滑膜、软骨和软骨下骨的细胞外间质的降解中充当重要角色。金属蛋白酶组织抑制剂-1(tissue inhibitors of metalloproteinase1,TIMP-1)与MMP-3特异结合,抑制MMP-3的活性,MMP-3/TIMP-1平衡对RA的临床结局有着重要作用。新的研究发现,抑制Th17细胞分化,维持Treg细胞(regulatory T cell)活性,调节Th17/Treg平衡,可为治疗RA提供新的作用靶点。进一步研究发现,RA早期患者外周血MMP-3与白介素17(Interleukin17,IL-17)表达明显升高,两者呈正相关,Treg的下降可影响MMP-3/TIMP-1的平衡。本文将对MMP-3/TIMP-1和Th17/Treg在RA中的作用机制及其临床意义作一综述。

大动脉炎患者外周血Th17/Treg细胞及相关细胞因子的表达

目的研究大动脉炎(takayasu arteritis,TA)患者外周血辅助性T细胞17(Th17细胞)、调节性T细胞(Treg细胞)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白细胞介素-17(IL-17)及肿瘤坏死因子-α(TNF-a)的表达及其与疾病活动的关系。方法入组大动脉炎患者46例,及性别年龄均相匹配的健康人43例,根据美国卫生研究所(NIH)标准判断所有患者疾病活动情况,其中TA活动组30例,非活动组16例。采用流式细胞仪技术(FCM)检测所有受试者外周血Th17、Treg细胞计数及比例,采用流式液相多重蛋白定量技术(CBA)检测外周血细胞因子,并做统计分析。结果与健康对照组比较,TA活动组、非活动组外周血Th17细胞绝对计数和相对计数明显上升,Treg细胞绝对计数和相对计数显著下降,Th17/Treg比值增大,差异有统计学意义(P<0.05)。与非活动组比较,TA活动组IL-6JL-17和TNF-a明显升高,IL-10明显减少,差异有统计学意义(P<0.05);与非活动组比较,TA疾病活动组Th 17细胞有升高趋势和Treg细胞表达下降,差异无统计学意义(P>0.05).ROC结果显示,IL-6、IL-10 JL-17和TNF-a预测TA活动的曲线下面积(area under curve,AUC)分别为0.806,0.694,0.704和0.767。结论大动脉炎患者外周血Th17细胞、Treg细胞以及Th17/Treg比值与其发病相关,与疾病活动无明显相关性;IL-6JL-10.IL-17和TNF-α可预测TA的疾病活动。

Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice

AIM: To determine the therapeutic efficacy of resveratrol on ulcerative colitis (UC) and its underlying mechanisms. METHODS: The mouse UC model was developed using 5% dextran sulfate sodium. Mice were randomly divided into four groups: normal control, UC model group, resveratrol low-dose group (RLD; 50 mg/kg per day), and resveratrol high-dose group (RHD; 100 mg/kg per day). RESULTS: The results showed that RLD regulates Treg/Th17 balance mainly through reducing the number of Th17 cells, whereas RHD regulates Treg/Th17 balance through both downregulating the number of Th17 cells and upregulating the number of Treg cells. Resveratrol can also regulate the level of plasma and intestinal mucosal cytokines including interleukin (IL)-10, transforming growth factor-beta 1, IL-6, and IL-17. The expressions of hypoxia inducible factor (HIF)-1 alpha, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 were significantly decreased in the intestinal tissues of mice treated with resveratrol. CONCLUSION: The therapeutic efficacy of resveratrol in UC is dose dependent and closely associated with the regulation of Treg/Th17 balance and the HIF-1 alpha/mTOR signaling pathway.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

神经注射治疗术联合益气活血止痛汤治疗带状疱疹后遗神经痛的疗效及其对Th17/Treg细胞平衡和炎症因子的影响

目的:探究神经注射治疗术联合益气活血止痛汤治疗带状疱疹后遗神经痛(PHN)的疗效及其对辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡和炎症因子的影响。方法:将300例PHN患者按不同治疗方式分为对照组和观察组,每组各150例。对照组予以神经妥乐平注射治疗;观察组在对照组的基础上增加益气活血止痛汤治疗。比较两组临床疗效及治疗前后中医证候积分[灼烧感、瘙痒感]、疼痛[疼痛视觉模拟评分(VAS)]、睡眠质量[匹兹堡睡眠质量指数(PSQI)]、Th17/Treg细胞平衡[Th17、Treg及Th17/Treg]及炎症因子[白细胞介素-6(IL-6)、IL-10、肿瘤坏死因子-α(TNF-α)]水平。结果:观察组临床总有效率高于对照组(91.33%vs.82.00%,P<0.05)。治疗后,观察组灼烧感、瘙痒感评分及VAS、PSQI评分均低于对照组(P<0.05)。与对照组相比,观察组治疗后Th17、Treg、Th17/Treg及血清IL-6、TNF-α水平更低,血清IL-10水平则更高(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(8.00%vs.9.33%,P>0.05)。结论:神经注射治疗术联合益气活血止痛汤治疗PHN的疗效和安全性俱佳,可缓解患者灼烧感、瘙痒感、疼痛症状,改善睡眠质量,调节Th17/Treg细胞平衡与IL-6、IL-10、TNF-α水平可能是其作用机制之一。

Th17、Treg细胞及其相关细胞因子对溃疡性结肠炎发病的影响

目的:研究Th17、Treg细胞及其相关细胞因子对溃疡性结肠炎发病的影响。方法:选取2013年6月~2016年7月在同济医院消化内科明确诊断为溃疡性结肠炎患者78例为病例组,选择同期因腹痛、腹泻或体质量减轻在消化内科经胃肠镜等相关检查排除消化道器质性病变的患者52例为对照组,采用流式细胞仪检测2组患者外周血中Th17、Treg细胞的比例,采用ELISA法检测2组患者外周血中IL-17、IL-10的表达水平。结果:病例组患者外周血中Th17细胞比例较对照组升高,Treg细胞比例较对照组降低,同时Th17/Treg比值较对照组升高(P<0.05);随着病情的加重,病例组患者Th17细胞在外周血中的比例逐渐升高,Treg细胞在外周血中的比例逐渐降低,Th17/Treg比值也逐渐升高(P<0.05);IL-17在外周血中的水平逐渐升高(P<0.05),而IL-10在外周血中的水平逐渐降低(P<0.05)。病例组患者外周血中IL-17水平较对照组升高,IL-10水平较对照组降低(P<0.05)。结论:溃疡性结肠炎患者中存在Th17、Treg细胞比例失衡,这可能是溃疡性结肠炎发病的免疫原因之一,维持Th17/Treg细胞的平衡,是防止溃疡性结肠炎发生的途径之一。