Th17/Treg细胞失衡与子宫颈癌

Th17细胞是近年发现的一种新型CD4^＋效应性T细胞,以其特异性的分泌IL-17而命名。介导免疫耐受的Treg细胞和介导炎症反应的Th17细胞间功能和分化过程相互对抗,在正常状态下,两者保持平衡,但机体发生功能异常时常表现出Treg/Th17失衡,引起炎性反应、自身免疫性疾病、移植物抗宿主病等的发生和发展,并决定疾病的转归和预后,在肿瘤免疫中亦发挥了重要作用。该文就Treg/Th17失衡在肿瘤,尤其是子宫颈癌发生发展中的作用进行综述。     

Th17/Treg失衡与肝脏免疫病理反应的研究进展

Th17细胞及Th17/Treg失衡在炎症反应、组织损伤及纤维化形成中发挥了重要作用,与多种疾病的发生发展密切相关。前炎性细胞因子可诱导T细胞分化为Th17,使Th17/Treg失衡,导致IL-17、IL-6、趋化因子等促炎性细胞因子大量分泌并有效介导中性粒细胞动员与兴奋,使得机体产生炎症反应与免疫病理反应。就Th17/Treg细胞及其失衡在肝脏免疫病理反应中的研究进展进行了综述。     

Decreased expression of microRNA‐21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis

The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3⁺CD4⁺IL‐17⁺Th17 cells were significantly higher, and CD4⁺CD25⁺FOXP3⁺ Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro‐inflammatory cytokines, including IL‐17, IL‐6, IL‐1β, TNF‐α and IL‐22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR‐21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up‐regulated miR‐21 expression from healthy controls, but down‐regulated miR‐21 expression from RA patients. Therefore, we speculate that miR‐21 may be part of a negative feedback loop in the normal setting. However, miR‐21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR‐21 may thus serve as a novel regulator in T‐cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.     

Exosomal microRNA-155-5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin-1 in chronic periodontitis

The mechanism of local inflammation and systemic injury in chronic periodontitis is complicated, in which and exosomes play an important role. In our study, we found that T helper cell 17 (Th17)/regulatory T cell (Treg) balance is destabilized in the peripheral blood of patients with periodontitis, with upregulated Th17 or downregulated Treg, respectively. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment of chronic periodontitis. The exosomes were extracted from periodontal ligament stem cells (PDLSCs) in LPS-induced periodontitis environment, which inversely effected on CD4+ T cells under normal and inflammatory conditions. Furthermore, compared with exosomes from normal PDLSCs, lower expression of microRNA-155-5p (miR-155-5p) and higher expression of Sirtuin-1 (SIRT1) were observed in exosomes from LPS-stimulated PDLSCs. Exosomes from PDLSCs alleviated inflammatory microenvironment through Th17/Treg/miR-155-5p/SIRT1 regulatory network. This study aimed to find the “switching” factors that affected the further deterioration of periodontitis to maximally control the multiple downstream damage signal factors to further understand periodontitis and find new targets for its treatment.     

肺炎支原体肺炎伴喘息儿童血清25(OH)D_3、Th17/Treg表达水平与肺功能的关系

目的:探讨肺炎支原体肺炎伴喘息儿童血清25羟基维生素D3[25(OH)D_3]、辅助性17细胞/调节性T细胞(Th17/Treg)表达水平与肺功能的关系。方法:将新疆医科大学第五附属医院收治的肺炎支原体肺炎伴喘息患儿26例作为肺炎伴喘息组,肺炎支原体肺炎不伴有喘息患儿54例作为肺炎不伴喘息组,另选取健康儿童30例作为对照组,比较各组血清25(OH)D_3、白细胞介素(IL)-10、IL-17、Th17细胞及Treg细胞占CD4+T细胞比例及肺功能,并分析其相关性。结果:肺炎伴喘息组血清25(OH)D_3、IL-10、Treg细胞占CD4+T细胞比例低于肺炎不伴喘息组、对照组,Th17细胞占CD4+T细胞比例、Th17/Treg、IL-17高于肺炎不伴喘息组、对照组(P0.05)。各组第一秒最大呼气量占用力肺活量百分比(FEV1/FVC)比较差异无统计学意义(P0.05),肺炎伴喘息组FEV1占预计值百分比(FEV1%pred)、峰值呼气流量(PEF)低于肺炎不伴喘息组、对照组(P0.05),肺炎不伴喘息组与对照组FEV1%pred、PEF比较无统计学意义(P0.05)。肺炎伴喘息组患儿血清25 (OH)D_3与Th17/Treg、IL-17呈负相关(P0.05),与IL-10、FEV1%pred、PEF呈正相关(P0.05),血清Th17/Treg与IL-10、FEV1%pred、PEF呈负相关(P0.05),与IL-17呈正相关(P0.05)。结论:肺炎支原体肺炎伴喘息儿童血清25(OH)D_3、Th17/Treg表达水平异常,肺功能下降,且25(OH)D_3、Th17/Treg表达水平与肺功能相关。     

间充质干细胞对Th17/Treg平衡的影响及与IBD的关系

辅助性T细胞17（Th17）/调节性T细胞（Treg）失衡是炎症性肠病（IBD）发病的重要因素,纠正Th17/Treg细胞失衡可以减缓或抑制IBD的发生发展,成为治疗IBD的靶点。间充质干细胞具有抗炎及免疫调节功能,通过可溶性因子、细胞接触及外泌体的方式调节适应性和先天性免疫,纠正Th17/Treg失衡缓解IBD,这给IBD的治疗提供新的方向。目前,MSCs和IBD的关系研究较少,本文综述了MSCs调节Th17/Treg平衡及与IBD的关系。     

Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis by Regulating Th17/Treg Cell Balance

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn''s disease, is a group of autoimmune diseases characterized by nonspecific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a wide range of anti-inflammatory and immune regulatory function, which exerts significantly protective roles in various T cell-mediated diseases. In this study, we aim to explore the immunological regulation of HO-1 in the dextran sulfate sodium-induced model of experimental murine colitis. BALB/c mice were administered 4% dextran sulfate sodium orally; some mice were intraperitoneally pretreated with HO-1 inducer hemin or HO-1 inhibitor stannum protoporphyrin IX. The results show that hemin enhances the colonic expression of HO-1 and significantly ameliorates the symptoms of colitis with improved histological changes, accompanied by a decreased proportion of Th17 cells and increased number of Tregs in mesenteric lymph node and spleen. Moreover, induction of HO-1 down-regulates retinoic acid-related orphan receptor γt expression and IL-17A levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10 levels in colon. Further study in vitro revealed that up-regulated HO-1 switched the naive T cells to Tregs when cultured under a Th17-inducing environment, which involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory activity in the murine model of acute experimental colitis via regulating the balance between Th17 and Treg cells, thus providing a possible novel therapeutic target in IBD.     

染色体核型异常、Th17/Treg免疫失衡与复发性流产的关系及其影响因素分析

摘要 目的：研究染色体核型异常、辅助性T细胞17（Th17）/调节性T细胞（Treg）免疫失衡与复发性流产（RSA）的关系及其影响因素。方法：选择石家庄市妇幼保健院从2019年2月～2022年2月收治的421例RSA患者,记作研究组。另取同期无生殖系统异常女性400例作为对照组。比较两组染色体核型异常、Th17/Treg免疫情况以及各项基线资料。采用多因素Logistic回归分析明确RSA的影响因素。结果：研究组染色体核型异常发生率为10.21%,高于对照组的1.50%（P＜0.05）。研究组Th17、Th17/Treg比值高于对照组,而Treg低于对照组（均P＜0.05）。研究组文化程度初中及以下、生殖道感染、难闻性气味以及噪音人数占比均高于对照组（均P＜0.05）。经多因素Logistic回归分析可得：RSA的危险因素有文化程度初中及以下、生殖道感染、难闻性气味、噪音、染色体核型异常、Th17/Treg比值升高（均P＜0.05）。结论：染色体核型异常以及Th17/Treg免疫失衡均会增加RSA的发生风险,且文化程度初中及以下、生殖道感染、难闻性气味、噪音亦会增加RSA的发生风险,临床工作中可根据上述因素制定针对性干预措施,以达到降低RSA发生率的目的。     

免疫平衡的重要调节者白细胞介素-21

白细胞介素-21（IL-21）是γc家族的一个新成员,主要由活化的CD4＋ T细胞产生,对多种表达IL-21受体（IL-21R）的细胞如T细胞、B细胞、NK细胞及DC细胞等均有作用。近年发现IL-21与Th细胞系中新发现的分支Th17细胞的发生密切相关,在调节CD4＋ T细胞究竟是分化为Th17细胞还是CD4＋CD25＋Foxp3＋ Treg细胞中有＂开关＂作用,从而对免疫系统发挥重要的调节作用,在自身免疫性疾病和抗肿瘤免疫中扮演着重要的角色。简要综述了IL-21与Th17细胞、CD4＋CD25＋Foxp3＋ Treg细胞之间的关系及对免疫平衡的调节作用。     

大柴胡汤对轻症急性胰腺炎患者Th17/Treg免疫平衡和血清水通道蛋白的影响

摘要 目的：观察大柴胡汤对轻症急性胰腺炎（MAP）患者辅助性T细胞17 /调节性T细胞（Th17/Treg）免疫平衡和血清水通道蛋白（AQP）的影响。方法：按照随机数字表法，将天津中医药大学第一附属医院2020年4月~2022年4月期间收治的95例MAP患者分为对照组（西医基础治疗，47例）和研究组（对照组基础上接受大柴胡汤治疗，48例）。对比两组中医证候积分、Th17/Treg免疫平衡、AQP1、AQP5、AQP6和实验室指标。结果：两组治疗7 d后两胁胀痛，矢气则舒，右中上腹痛，恶心呕吐，抑郁易怒，嗳气呃逆，大便不畅评分均下降，且研究组低于对照组（P<0.05）。两组治疗7 d后Treg细胞比例升高，Th17细胞比例、Th17/Treg下降，且研究组的改善幅度大于对照组（P<0.05）。两组治疗7 d后AQP1、AQP5、AQP6升高，且研究组高于对照组（P<0.05）。两组治疗7 d后淀粉酶（AMY）、脂肪酶（LIP）、C反应蛋白（CRP）下降，且研究组低于对照组（P<0.05）。结论：大柴胡汤治疗MAP疗效确切，可以缓解患者的临床症状，有效改善MAP患者Th17/Treg免疫平衡和血清AQP1、AQP5、AQP6水平。     

Osteoimmunology: The correlation between osteoclasts and the Th17/Treg balance in osteoporosis

Osteoporosis is a bone disease that is caused by disorder of the skeletal microenvironment, and it characterized by a high disability rate and the occurrence of low energy fractures. Studies on osteoporosis and related treatment options have always been hot spots in the field of bone biology. In the past, the understanding of osteoporosis has been rather limited; research has only shown that osteoporosis involves the imbalance of bone resorption and bone formation, and recent studies have not provided cutting‐edge theories of the basic understanding of osteoporosis. Recent studies have shown crosstalk between bone and immune responses. RANKL, an essential factor for osteoclasts (OCs), is associated with the immune system. T helper (Th17)/regulatory T (Treg) cells are two different kinds of T cells that can self‐interact and regulate the differentiation and formation of OCs. Therefore, understanding the correlation between the skeletal and immune systems and further revealing the roles and the cooperation between RANKL and the Th17/Treg balance will help to provide new insights for the treatment of osteoporosis.     

Th17细胞和Treg细胞的细胞因子调节网络

Th17细胞和Treg细胞是CD4+T细胞的新亚群,在分化发育、功能发挥的过程中受到Th1型、Th2型效应细胞以及自身分泌产生细胞因子的调节,参与自身免疫病、感染、肿瘤等疾病的发生发展。通过对Th17和Treg分化发育、和功能发挥过程中的关键调节因子进行阻断或加强,可以上调或下调Th17和Treg在疾病中的表达,以用于疾病的预防和诊治。     

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。     

Th17/Treg 细胞在银屑病的发病机制研究进展

Th17细胞和Treg细胞是CD4+T细胞在不同细胞因子环境中分化出的新亚群,发挥不同的生物学效应,使机体的免疫系统处于平衡状态.Th17/Treg细胞失衡可引起一系列自身免疫性疾病.银屑病是与遗传、免疫异常有关的皮肤炎症性疾病,其发病机制尚不清楚.越来越多的研究发现,Th17细胞增多和Treg细胞减少及其分泌的细胞因子在银屑病的发病中有着重要作用.本文围绕这一机制综述了近年来有关Th17细胞、Treg细胞在银屑病发病机制中作用的研究,帮助我们更深入地了解银屑病的发病机制并为今后临床诊断和治疗提供依据.