Oukka M
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ann Rheum Dis. 2008 Dec;67 Suppl 3:iii26-9. doi: 10.1136/ard.2008.098004.
The primary function of Th17 cells appears to be the clearance of extracellular pathogens during infections. However, Th17 cells also promote inflammation and have been implicated in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions. Transforming growth factor beta (TGFbeta) is a critical differentiation factor for the generation of regulatory T (T-reg) cells, whereas the combination of interleukin 6 (IL6) and TGFbeta induces the differentiation of pathogenic Th17 cells. Therefore, it is proposed that at the steady state (in the absence of any inflammatory stimuli), TGFbeta, which is produced by various cells types including naturally occurring T-reg (nT-reg) cells, encourages the generation of induced T-reg (iT-reg) cells, which together with nT-reg cells keep autoreactive T cells under check. IL6, an acute phase protein produced by the activated immune system, inhibits the function of T-reg cells and instead promotes the differentiation of Th17 cells. Thus, IL6 plays a pivotal role in dictating the balance between the generation of T-reg and Th17 cells. This reciprocal relationship between T-reg and Th17 cells is further supported by the results obtained in IL6(-/-) mice, which show a severe defect in the generation of Th17 cells and increased numbers of T-reg cells in the peripheral repertoire.
Th17细胞的主要功能似乎是在感染期间清除细胞外病原体。然而，Th17细胞也会促进炎症反应，并且与许多实验性自身免疫性疾病和人类炎症性疾病的发病机制有关。转化生长因子β（TGFβ）是调节性T（T-reg）细胞生成的关键分化因子，而白细胞介素6（IL6）和TGFβ的组合则诱导致病性Th17细胞的分化。因此，有人提出，在稳态（无任何炎症刺激）下，由包括天然存在的T-reg（nT-reg）细胞在内的各种细胞类型产生的TGFβ会促进诱导性T-reg（iT-reg）细胞的生成，iT-reg细胞与nT-reg细胞一起控制自身反应性T细胞。IL6是激活的免疫系统产生的一种急性期蛋白，它会抑制T-reg细胞的功能，转而促进Th17细胞的分化。因此，IL6在决定T-reg细胞和Th17细胞生成之间的平衡中起关键作用。T-reg细胞和Th17细胞之间的这种相互关系在IL6基因敲除（IL6(-/-)）小鼠中得到的结果进一步得到支持，这些小鼠显示出Th17细胞生成存在严重缺陷，外周库中T-reg细胞数量增加。
