Chen Zhi, O'Shea John J
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, Musculoskeletal and Skin Diseases, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Immunol Res. 2008;41(2):87-102. doi: 10.1007/s12026-007-8014-9.
Classically naïve CD4(+) have been thought to differentiate into two possible lineages, T helper 1 (Th1) or T helper 2 (Th2) cells. Within this paradigm the pathogenesis of autoimmunity was suggested to predominantly relate to Th1 cells and the production of IFN-gamma. However, there were many aspects of this model that did not seem to fit, not the least of which was that IFN-gamma was protective in some models of autoimmunity. During the past 2 years, remarkable progress has been made to characterize a new lineage of helper T cells. Designated Th17 cells, this lineage selectively produces proinflammatory cytokines including IL-17, IL-21, and IL-22. In the mouse, the differentiation of this new lineage is initiated by TGFbeta-1 and IL-6 and IL-21, which activate Stat3 and induce the expression of the transcription factor retinoic acid-related orphan receptor (RORgammat). IL-23, which also activates Stat3, apparently serves to maintain Th17 cells in vivo. In human cells, IL-1, IL-6, and IL-23 promote human Th17 differentiation, but TGFbeta-1 is reportedly not needed. Emerging data have suggested that Th17 plays an essential role in the host defense against extracellular bacteria and fungi and in pathogenesis of autoimmune diseases. Selectively targeting the Th17 lineage may be beneficial for the treatment of inflammatory and autoimmune diseases.
传统上，初始CD4(+)细胞被认为可分化为两种可能的谱系，即辅助性T细胞1（Th1）或辅助性T细胞2（Th2）。在这一范式中，自身免疫性疾病的发病机制主要被认为与Th1细胞及γ干扰素的产生有关。然而，该模型存在许多似乎并不相符的方面，其中最明显的一点是，γ干扰素在某些自身免疫性疾病模型中具有保护作用。在过去两年中，在鉴定一种新的辅助性T细胞谱系方面取得了显著进展。这种谱系被命名为Th17细胞，它选择性地产生包括白细胞介素-17、白细胞介素-21和白细胞介素-22在内的促炎细胞因子。在小鼠中，这种新谱系的分化由转化生长因子β-1、白细胞介素-6和白细胞介素-21启动，它们激活信号转导及转录激活因子3（Stat3）并诱导转录因子视黄酸相关孤儿受体（RORγt）的表达。同样激活Stat3的白细胞介素-23显然在体内维持Th17细胞。在人类细胞中，白细胞介素-1、白细胞介素-6和白细胞介素-23促进人类Th17细胞分化，但据报道不需要转化生长因子β-（此处原文有误，推测为β-1）。新出现的数据表明，Th17在宿主抵御细胞外细菌和真菌的防御反应以及自身免疫性疾病的发病机制中起重要作用。选择性地靶向Th17谱系可能对炎症性和自身免疫性疾病的治疗有益。
