Takatori Hiroaki, Kanno Yuka, Chen Zhi, O'Shea John J
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mod Rheumatol. 2008;18(6):533-41. doi: 10.1007/s10165-008-0099-z. Epub 2008 Aug 5.
Recently, new complexities in cell fate decision for helper T cells have emerged. One new lineage, which has come to be called Th17 cells, selectively produces proinflammatory cytokines including interleukin-17 (IL-17, A and F), IL-21, and IL-22. In conjunction with transforming growth factor beta-1 (TGFbeta-1), IL-6, IL-21, and IL-23, which activate the transcription factor, signal transducer, and activator of transcription 3 (Stat3), the expression of another transcription factor, retinoic acid-related orphan receptor-gammat (RORgammat) leads to the differentiation of Th17 cells in mice. Other cytokines including IL-2, IL-4, interferon-gamma (IFN-gamma), and IL-27 inhibit Th17 differentiation. However, IL-2 acting with TGFbeta-1 induces differentiation of naïve CD4+ T cells to become regulatory T cells (Tregs). Th17 cells are now known to play an important role not only in the pathogenesis of inflammation and autoimmune diseases, but also host defense against extracellular bacteria. Conversely, extensive data substantiate the role of Tregs as essential in maintenance of peripheral tolerance. Selectively targeting Tregs and Th17 cells are likely to be important strategies in the treatment of inflammatory and autoimmune diseases in humans.
最近，辅助性T细胞在细胞命运决定方面出现了新的复杂性。一种新的细胞谱系，即现在所称的Th17细胞，可选择性地产生促炎细胞因子，包括白细胞介素-17（IL-17，A和F）、IL-21和IL-22。与转化生长因子β-1（TGFβ-1）、IL-6、IL-21和IL-23共同作用时，这些因子可激活转录因子、信号转导子和转录激活子3（Stat3），另一种转录因子维甲酸相关孤儿受体γt（RORγt）的表达会导致小鼠体内Th17细胞的分化。其他细胞因子，包括IL-2、IL-4、干扰素-γ（IFN-γ）和IL-27可抑制Th17细胞的分化。然而，IL-2与TGFβ-1共同作用可诱导初始CD4+T细胞分化为调节性T细胞（Treg）。现在已知Th17细胞不仅在炎症和自身免疫性疾病的发病机制中起重要作用，而且在宿主抵御细胞外细菌方面也发挥重要作用。相反，大量数据证实Treg在维持外周耐受中起关键作用。选择性靶向Treg和Th17细胞可能是治疗人类炎症和自身免疫性疾病的重要策略。
