Lochner Matthias, Wang Zuobai, Sparwasser Tim
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research: A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research: A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Prog Mol Biol Transl Sci. 2015;136:99-129. doi: 10.1016/bs.pmbts.2015.07.013. Epub 2015 Aug 18.
T helper 17 (Th17) cells play an essential role in the clearance of extracellular pathogenic bacteria and fungi. However, this subset is critically involved in the pathology of many autoimmune diseases, e.g., psoriasis, multiple sclerosis, allergy, rheumatoid arthritis, and inflammatory bowel diseases in humans. Therefore, Th17 responses need to be tightly regulated in vivo to mediate effective host defenses against pathogens without causing excessive host tissue damage. Foxp3(+) regulatory T (Treg) cells play an important role in maintaining peripheral tolerance to self-antigens and in counteracting the inflammatory activity of effector T helper cell subsets. Although Th17 and Treg cells represent two CD4(+) T cell subsets with opposing principal functions, these cell types are functionally connected. In this review, we will first give an overview on the biology of Th17 cells and describe their development and in vivo function, followed by an account on the special developmental relationship between Th17 and Treg cells. We will describe the identification of Treg/Th17 intermediates and consider their lineage stability and function in vivo. Finally, we will discuss how Treg cells may regulate the Th17 cell response in the context of infection and inflammation, and elude on findings demonstrating that Treg cells can also have a prominent function in promoting the differentiation of Th17 cells.
辅助性T细胞17(Th17细胞)在清除细胞外致病细菌和真菌方面发挥着重要作用。然而,这一亚群在许多自身免疫性疾病的病理过程中起着关键作用,例如人类的银屑病、多发性硬化症、过敏、类风湿性关节炎和炎症性肠病。因此,Th17反应在体内需要受到严格调控,以介导宿主对病原体的有效防御,同时又不会对宿主组织造成过度损伤。Foxp3(+)调节性T(Treg)细胞在维持对外源性抗原的外周耐受性以及对抗效应性辅助性T细胞亚群的炎症活性方面发挥着重要作用。尽管Th17细胞和Treg细胞代表了两个具有相反主要功能的CD4(+) T细胞亚群,但这些细胞类型在功能上是相互关联的。在这篇综述中,我们首先将概述Th17细胞的生物学特性,并描述它们的发育过程和体内功能,接着阐述Th17细胞和Treg细胞之间特殊的发育关系。我们将描述Treg/Th17中间态的鉴定,并探讨它们在体内的谱系稳定性和功能。最后,我们将讨论Treg细胞在感染和炎症背景下如何调节Th17细胞反应,并提及一些研究结果,这些结果表明Treg细胞在促进Th17细胞分化方面也可能具有重要作用。