Th17细胞及白细胞介素-17在肝移植急性排斥反应中的意义

目的探讨Th17细胞及相关因子白细胞介素-17（IL-17）在肝移植急性排斥反应中的变化及意义。方法收集2011年1月至2012年12月大连医科大学附属第二医院肝移植手术患者28例,根据移植肝组织穿刺活检病理诊断结果将肝移植的28例患者分为急性排异反应组6例和无排斥反应稳定组22例,15名健康体检者作为对照组。急性排斥组及稳定组在移植术后3 d和7 d,行肝穿刺活检病理检查;同时检测受检者外周血Th17细胞,受检者血清中IL-17水平。结果移植肝穿刺活检病理诊断显示急性排斥组随着移植时间延长,排斥反应逐渐增强。肝组织出现典型的细胞免疫性病理损伤,术后7 d肝脏汇管区、肝实质、小静脉壁、胆管上皮内及小叶间胆管被大量的淋巴细胞及嗜中性粒细胞包绕及浸润,胆管上皮细胞内空泡形成、上皮细胞凋亡。病理改变明显比术后3 d严重;急性排斥组患者术后3 d和7 d外周血Th17细胞比例及血清中IL-17含量较稳定组和对照组均明显增多（P〈0.05）,且Th17细胞及IL-17在术后急性排斥期7 d值均明显高于3 d（P〈0.05）。结论 Th17细胞及IL-17在肝移植急性排斥反应的发生、发展中可能起着促进作用,外周血Th17细胞及IL-17的检测有可能成为肝移植急性排斥反应的早期诊断指标。     

急性发作支气管哮喘患儿粪便菌群特征及其与Th17细胞免疫功能的关系CSCD

目的 研究急性发作支气管哮喘儿童粪便菌群特征及其与Th17细胞免疫功能的关系,为该类患儿的治疗提供参考。方法 选择2019年12月至2020年12月我院收治的96例急性发作支气管哮喘患儿为研究组,选择同期来我院进行粪便检查并结果正常的60例健康体检儿童为对照组。对比两组对象粪便菌群分布情况,外周血TGF-β_(1)、IL-17、Th17细胞、Treg细胞、Th17/Treg水平。采用Pearson相关分析患儿粪便菌群数量与Th17细胞免疫功能的相关性。结果 研究组患儿粪便中大肠埃希菌数量显著高于对照组,而乳杆菌和双歧杆菌数量显著低于对照组(均P<0.05)。研究组患儿外周血TGF-β_(1)、 IL-17、 Th17细胞、Th17/Treg水平显著高于对照组,而Treg细胞水平显著低于对照组(均P<0.05)。Pearson相关分析表明,哮喘患儿粪便大肠埃希菌数量与外周血TGF-β_(1)、 IL-17、 Th17细胞、 Th17/Treg水平呈正相关(r=0.528、0.714、0.524、0.572,均P<0.05),与外周血Treg细胞水平呈负相关(r=-0.439,P<0.05)。哮喘患儿粪便乳杆菌数量与外周血Treg细胞水平呈正相关(r=0.459, P<0.05),与外周血TGF-β_(1)、 IL-17、 Th17细胞、Th17/Treg水平呈负相关(r=-0.457、-0.692、-0.491、-0.563,均P<0.05)。哮喘患儿粪便双歧杆菌数量与外周血Treg细胞水平呈正相关(r=0.462,P<0.05),与外周血TGF-β_(1)、IL-17、Th17细胞、Th17/Treg水平呈负相关(r=-0.496、-0.729、-0.542、-0.558,均P<0.05)。结论 急性发作支气管哮喘患儿肠道优势菌数量减少,肠道机会致病菌数量增加,并与Th17细胞免疫功能存在一定联系。     

良性前列腺增生患者外周血Th17和Treg细胞比率的变化

目的:探讨良性前列腺增生患者外周血Th17和Treg细胞比率的变化。方法:选择33例良性前列腺增生患者及19例正常对照者为研究对象,采用流式细胞术检测和比较其外周血中T淋巴细胞亚群及Th17和Treg细胞占CD4~+T细胞的比率。结果:良性前列腺增生患者外周血Th17和Treg细胞占CD4~+T细胞的比率分别为1.58±0.71和1.76±0.83,Th17/Treg的比率为0.89±0.42。正常健康对照者外周血Th17和Treg细胞占CD4~+T细胞的比率分别为0.75±0.46和1.83±0.75,Th17/Treg的比率为0.41±0.32。良性前列腺增生患者外周血Th17占CD4~+T细胞的比率和Th17/Treg的比率明显高于正常健康对照者(P0.05)。结论:良性前列腺增生患者体内Th17细胞比率升高,Th17/Treg比率失衡,可能与良性前列腺增生的发生、发展有关。     

细胞免疫功能及辅助型T细胞因子在口腔扁平苔藓中的作用

目的探讨细胞免疫功能及辅助型T细胞(Th)细胞因子在口腔扁平苔藓(OLP)中的作用。方法以35例糜烂型(糜烂组)及29例网纹型OLP(网纹组)患者为对象,选取同期20例健康人为对照组,流式细胞术检测外周血中T细胞、B细胞、NK细胞和调节性T细胞亚群表达百分率。ELISA法检测外周血中TNF-α和INF-γ(Th1型细胞因子),IL-4和IL-10(Th2型细胞因子),IL-17、IL-23(Th17型细胞因子)含量;分离外周血单个核细胞,qRT-PCR检测上述因子mRNA的表达。结果与健康组相比,OLP患者CD3~+、CD4~+T细胞亚群比例(F=3.211和3.565,P0.05)及CD4~+/CD8~+降低(F=3.430,P0.05),CD4~+Foxp3~+调节性T细胞亚群比例(F=3.370,P0.05)及外周血中TNF-α、INF-γ、IL-4、IL-10、IL-17、IL-23含量增高(F=0.923、0.820、1.043、1.132、0.745和0.802,P0.05)。与网纹组相比,糜烂组CD8~+T细胞亚群比例较低(t=2.450,P0.05);IL-4、IL-10蛋白(t=22.780和25.112,P0.05)及mRNA较低(t=3.781和6.710,P0.05),IL-17、IL-23蛋白(t=15.765和19.307,P0.05)及mRNA较高(t=4.022和8.569,P0.05)。结论口腔扁平苔藓患者存在细胞免疫紊乱及Th细胞因子异常,其中CD8~+及Th17型细胞与糜烂型OLP发病有关,Th2型细胞与网纹型OLP发病有关。     

大鼠肝移植急性排斥反应模型的建立与评价

目的：建立大鼠肝脏移植急性排斥反应模型,并对所建模型进行评价。方法：采用改良Kamada“二袖套”法,以近交系大鼠Dark Agouti（DA）为供体、Lewis（LEW）为受体（A组）建立大鼠原位肝移植急性排斥反应模型,通过观察手术情况、生存情况及肝功能和病理学检查对此模型进行评价,同时以LEW→LEW作为对照组（B组）。结果：手术成功率为91.3%;手术时间为（90.70±5.68）min;无肝期时间（9.96±1.19）min;平均存活时间A组为（12.44±3.43）d,B组超过100d;A组血清谷丙转氨酶、谷草转氨酶及血清总胆红素术后不断升高,在第10～14d最为明显,血清白蛋白在术后第3d开始逐渐降低,在相同时相点,与B组相比差异显著;A组移植肝脏病理检查有明显的排斥反应,而B组没有。结论：DA→LEW为稳定、强烈的大鼠肝移植急排模型,是研究肝移植排斥及免疫耐受的理想动物模型。     

益生菌对克罗恩病患者肠道屏障功能和免疫调节的影响

目的 研究益生菌对克罗恩病患者肠道屏障功能和免疫调节的影响,为该类患者的治疗提供参考。方法 选择2018年1月至2020年6月我院收治的94例克罗恩病患者进行前瞻性随机对照研究,根据住院尾号单双数随机分为单号的对照组（n=45）和双号的益生菌组（n=49）。对照组患者给予柳氮磺胺吡啶联合安慰剂治疗,益生菌组患者给予柳氮磺胺吡啶联合双歧杆菌三联活菌片治疗。治疗前及治疗后2个月时,分别检测患者粪便中肠道菌群数量,简化克罗恩病活动指数（CDAI）,血沉（ERS）,血清中超敏C反应蛋白（hs-CRP）、二胺氧化酶、D-乳酸、干扰素-γ(IFN-γ)、白介素（IL）-4、IL-10、IL-17的水平以及外周血中Th1、Th2、Th17、Treg细胞的数目。随访2组患者预后不良终点事件的累积发生率。结果 治疗后2个月,益生菌组患者粪便中拟杆菌、肠杆菌、肠球菌的数量,简化CDAI、ERS水平,血清中hs-CRP、二胺氧化酶、D-乳酸、IFN-γ、IL-17水平,外周血中Th1、Th17的数量均低于对照组;而粪便中双歧杆菌、乳杆菌数量,血清中IL-4、IL-10水平,外周血中Th2、Treg的数量均高...     

妊娠梅毒患者外周血中Th17和Treg细胞水平及其临床意义分析

目的:探讨妊娠梅毒患者外周血中Th17和Treg细胞水平及其临床意义。方法:选择2015年4月至2016年5月我院收治的35例妊娠梅毒患者作为观察组,并选择同期进行孕检的健康孕妇30例作为对照组。分析和比较其外周血Th17和Treg细胞水平及其诊断妊娠梅毒的临床价值。结果:观察组患者外周血Th17水平显著高于对照组,而外周血Treg水平显著低于对照组(P0.05)。多因素logistic回归分析结果显示外周血Th17和Treg水平与妊娠梅毒发病具有明显相关性。外周血Th17诊断妊娠梅毒的AUC为0.776,95%CI为0.656～0.896,外周血Treg诊断妊娠梅的ROC曲线下的面积(area under curve,AUC)为0.947,95%CI为0.897～997,Th17+Treg诊断妊娠梅毒的AUC为0.960,95%CI为0.913～1.000;Th17和Treg单独检测分别和联合检测曲线下面积比较均具有显著差异(Z=-2.807、-0.375,P0.05);Th17+Treg联合检测的特异度、准确度分别为91.73%、93.28%,显著高于各指标单独检测(P0.05)。结论:妊娠梅毒患者外周血Th17细胞增多,Treg细胞减少,联合检测外周血Th17和Treg细胞水平诊断妊娠梅毒具有较高的准确度,可作为诊断妊娠梅毒的重要参考指标。     

复发性自然流产患者外周血中Th17及Treg细胞及其效应因子的变化

目的:探讨复发性自然流产患者外周血中Th17、Treg细胞以及相关细胞因子的变化。方法:选择复发性自然流产患者25例,正常妊娠妇女25例以及正常非妊娠育龄妇女25例,流式细胞术测定外周血中Th17和Treg细胞数量,ELISA法测定血清IL-10、TGF-β及IL-17的浓度。结果:复发性自然流产患者外周血中Th17细胞百分率显著高于正常妊娠以及正常非孕妇女(P0.05),Treg细胞百分率显著低于正常非孕妇女(P0.05),但与正常妊娠妇女相比无显著性差异(P0.05);复发性自然流产患者外周血IL-10及TGF-β水平显著低于正常妊娠妇女以及正常非孕妇女(P0.05),而IL-17水平显著高于正常妊娠妇女以及正常非孕妇女(P0.05)。结论:外周血Th17细胞数和IL-17水平的升高以及抑制性细胞因子IL-10和TGF-β水平的下降可能是复发性自然流产发生的重要原因。     

晚期非小细胞肺癌患者外周血Th17细胞和Treg细胞水平与化疗敏感相关性研究

目的:探讨晚期非小细胞肺癌患者外周血Th17细胞和Treg细胞水平和化疗敏感性相关性。方法:2选取78例晚期非小细胞肺癌患者为病例组,同时纳入健康人群40例为对照组。病例组肺癌患者采用TP方案,化疗前后采用流式细胞计数检测外周血Th17(CD4~+γ-IFN~+)、Treg(CD4~+CD25~+Foxp3~+)水平,完成2个化疗疗程后,评价化疗效果及敏感性。结果:病例组外周血Th17细胞和Treg细胞水平明显高于对照组,差异有统计学意义(p0.05)。病例组第一次和第二次化疗前外周血Th17细胞和Treg细胞水平高于化疗后水平,差异有统计学意义(p0.05)。根据WHO实体肿瘤化疗效果判定标准,CR为化疗敏感组、PR、SD为化疗有效,PD为化疗无效,将所有病例组分为化疗敏感性组、有效组和无效。第一次化疗前和第二次化疗前外周血Th17细胞和Treg细胞水平,化疗敏感组水平明显高于有效组和无效组,而有效组水平高于无效组,差异有统计学意义(p0.05)。结论:肺癌患者晚期外周血Th17细胞和Treg细胞水平明显升高,其Th17细胞和Treg细胞水平和化疗敏感性呈正相关的趋势。     

血清炎症因子联合T淋巴细胞亚群在急性呼吸窘迫综合征中的应用价值分析

摘要 目的：分析血清炎症因子联合T淋巴细胞亚群在急性呼吸窘迫综合征中的应用价值。方法：选择我院2021年7月至2022年12月收治的70例急性呼吸窘迫综合征患者作为研究对象,分为轻度组、中度组和重度组。检测所有入选者的血清炎症因子、T淋巴细胞亚群,分析急性呼吸窘迫综合征患者血清炎症因子、T淋巴细胞亚群与氧合指数（OI）、肺部超声B线数目的关系;观察急性呼吸窘迫综合征患者28 d后预后情况,分为死亡组与存活组,使用ROC曲线分析血清炎症因子联合T淋巴细胞亚群对急性呼吸窘迫综合征患者死亡的预测效能。结果：血清IL-6、IFN-γ表达水平、外周血Th17细胞比例、Th17/Treg比值在轻度组、中度组和重度组中差异显著,两两比较,差异显著（P＜0.05）;经Pearson相关性分析,急性呼吸窘迫综合征患者血清IL-6、IFN-γ表达水平、外周血Th17细胞比例、Th17/Treg比值均与OI呈负相关,与B线数目呈正相关（P＜0.05）;死亡组血清IL-6、IFN-γ表达水平、外周血Th17细胞比例均高于存活组,Th17/Treg比值大于存活组,差异显著（P＜0.05）;经ROC曲线分析,IL-6、IFN-γ联合Th17/Treg比值预测急性呼吸窘迫综合征患者死亡的AUC为0.935。结论：血清炎症因子、T淋巴细胞亚群与急性呼吸窘迫综合征病情严重程度有关,其中IL-6、IFN-γ联合Th17/Treg比值预测预后不良的效能较好,值得临床予以重视应用。     

The Ratio of Circulating Regulatory T Cells (Tregs)/Th17 Cells Is Associated with Acute Allograft Rejection in Liver Transplantation

CD4⁺CD25⁺FoxP3⁺ regulatory T cells (Tregs) and Th17 cells are known to be involved in the alloreactive responses in organ transplantation, but little is known about the relationship between Tregs and Th17 cells in the context of liver alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is associated with acute allograft rejection in liver transplantation. In present study, thirty-eight patients who received liver transplant were enrolled. The patients were divided into two groups: acute allograft rejection group (Gr-AR) (n = 16) and stable allograft liver function group (Gr-SF) (n = 22). The frequencies of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were determined using flow cytometry. The association between Tregs/Th17 ratio and acute allograft rejection was then analyzed. Our results showed that the frequency of circulating Tregs was significantly decreased, whereas the frequency of circulating Th17 cells was significantly increased in liver allograft recipients who developed acute rejection. Tregs/Th17 ratio had a negative correlation with liver damage indices and the score of rejection activity index (RAI) after liver transplantation. In addition, the percentages of CTLA-4⁺, HLA-DR⁺, Ki67⁺, and IL-10⁺ Tregs were higher in Gr-SF group than in Gr-AR group. Our results suggested that the ratio of circulating Tregs/Th17 cells is associated with acute allograft rejection, thus the ratio may serve as an alternative marker for the diagnosis of acute rejection.     

Increased Numbers of Circulating CD8 Effector Memory T Cells before Transplantation Enhance the Risk of Acute Rejection in Lung Transplant Recipients

The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty-seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naïve T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8⁺ effector memory T cells over 185 cells/mm³ had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8⁺ effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection.     

Frequency of Th17 CD4+ T Cells in Early Rheumatoid Arthritis: A Marker of Anti-CCP Seropositivity

Objective

To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients.

Methods

CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants.

Results

When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC.

Conclusion

Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.     

自身免疫性肝病患者外周血Th1/Th2细胞的表达及其与肝功能的相关性研究

目的:探讨自身免疫性肝病(AILD)患者外周血中辅助T细胞1(Th1)和辅助T细胞2(Th2)的表达情况及其与肝功能的相关性。方法:选择42例AILD患者为实验组,11例健康体检者作为对照组,采用流式细胞术检测实验组和对照组外周血单个核细胞中Th1和Th2细胞在淋巴细胞亚群中所占百分率,并检测患者肝功能,分析Th1、Th2细胞水平与肝功能血清生化指标的相关性。结果:AILD组患者Th1细胞和Th2细胞百分率均高于健康对照组(P0.05);AILD活动期患者Th1和Th2细胞百分率明显高于健康对照组,AILD缓解期患者外周血淋巴细胞亚群中Th1细胞所占比例明显降低,Th2细胞百分率较健康人群高,Th1/Th2比值明显降低。AILD患者Th1细胞百分率与血清中TBIL、DBIL、GGT水平呈正相关关系(r分别为0.428、0.472、0.511,P值分别为0.010、0.004、0.002)。Th1/Th2比值与血清中TBIL、DBIL水平呈正相关关系(r分别为0.424、0.405,P值分别为0.011、0.016)。结论:AILD患者Th1细胞和Th2细胞百分率异常升高,且Th1细胞百分率及Th1/Th2比率与AILD患者肝功能指标具有良好的相关性。     

Aberrant Circulating Th17 Cells in Patients with B-Cell Non-Hodgkin’s Lymphoma

Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin’s lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease.     

变应性鼻炎患者外周血中Tr1/Th3细胞的检测和分析

目的:检测变应性鼻炎(Allergic rhinitis,AR)患者和健康对照者外周血中IL-10+CD4+T细胞、TGF-β+CD4+T细胞(分别代表Tr1细胞和Th3细胞的特性)的比例,并探讨其在AR发病中的意义,为AR的治疗提供临床参考。方法:分离19例对粉尘螨过敏的AR患者和19例健康对照者外周血单个核细胞(PBMCs),采用流式细胞术分别检测外周血中IL-10+CD4+T细胞、TGF-β+CD4+T细胞的比例。结果:同健康对照者相比,AR患者外周血中IL-10+CD4+T细胞的比例显著降低[(1.66±0.48)%vs.(3.80.92)%,t=-9.08,P0.01)],AR患者外周血中TGF-β+CD4+T细胞的比例降低[(1.92±0.54)%vs.(4.76±1.12)%,t=-9.94,P0.01)]。结论:外周血中IL-10+CD4+T(Tr1)细胞比例的降低可能是AR发病的一个重要因素,提高AR患者外周血中分泌IL-10的Tr1细胞的比例可能在AR的治疗中具有重要意义。外周血中TGF-β1+CD4+T(Th3)细胞的比例显著降低,可能是AR发病的一个重要因素。但TGF-β1与AR关系的研究较少,特别是外周血中TGF-β1水平与AR的关系研究较少,需进一步研究。     

Effect of Intestinal Microbiota Alteration on Hepatic Damage in Rats with Acute Rejection After Liver Transplantation

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer’s patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer’s patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.     

The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal

Objectives

Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients.

Methods

Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22) or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20). Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission.

Results

The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed.

Conclusions

An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The circulating Treg/Th17 ratio could serve as an alternative marker for monitoring pulmonary sarcoidosis relapse after the end of corticosteroid treatment and for rapidly predicting the response to retreatment.     

丹参对非酒精性脂肪肝Th17细胞及相关细胞因子的影响*

目的:研究丹参对非酒精性脂肪肝(NAFLD)大鼠Th17细胞及相关细胞因子的影响,为临床上丹参治疗NAFLD提供实验依据。方法:SPF级别SD大鼠32只,随机分为模型组、空白对照组、葛根对照组、丹参组,每组8只。模型组给予高脂饲料喂养4周以建立NAFLD模型;丹参治疗组及葛根对照组大鼠给予6.25g·kg^-1·d^-1的浓缩液每日1次灌胃;除了空白对照组外,其余各组大鼠均给予高脂饲料喂饲4周。实验完全结束(第4周),各组大鼠禁食12～14 h,禁水2 h后,采血,收集肝脏组织,检测各组大鼠血脂(TC、TG、LDL-C、HDL-C)水平及肝功能(AST、ALT)、肝脏指数,观察肝组织病理学改变。流式细胞仪检测外周血Th17、Treg细胞含量。通过ELISA法检测血清IL-6、IL-17、TNF-α水平;RT-PCR法检测肝脏组织RORγt基因表达。结果:连续4周喂养高脂饮食后,模型组大鼠肝脏发生脂肪变性,有大量炎症细胞浸润。与模型组相比,丹参治疗组、葛根对照组大鼠TC、TG、LDL-C、ALT、AST水平及肝脏指数明显低于模型组(P＜0.05),HDL-C水平明显高于模型组(P＜0.05)成功复制NAFLD大鼠模型。丹参治疗组大鼠外周血Th17细胞含量、IL-6、IL-17水平、大鼠RORγt基因表达量显著低于模型组及葛根对照组(P＜0.05);TNF-α水平低于模型组及葛根对照组;Treg细胞含量高于模型组(P＜0.05)及葛根对照组(P＞ 0.05);Treg/ Th17显著高于模型组及葛根对照组 (P＜0.05)。结论:丹参通过降低血清中IL-6、IL-17、TNF-α水平,抑制RORγt基因表达,降低外周血Th17细胞含量,升高Treg细胞含量,调整Th17/Treg平衡,从而抑制NAFLD发生发展。