通过信号转导和转录激活因子5（STAT5）的白细胞介素-2信号传导会抑制辅助性T细胞17的生成。
Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation.
作者信息
Laurence Arian, Tato Cristina M, Davidson Todd S, Kanno Yuka, Chen Zhi, Yao Zhengju, Blank Rebecca B, Meylan Françoise, Siegel Richard, Hennighausen Lothar, Shevach Ethan M, O'shea John J
机构信息
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Immunity. 2007 Mar;26(3):371-81. doi: 10.1016/j.immuni.2007.02.009.
Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset. Whereas STAT3 appeared to be a key positive regulator of RORgammat and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 resulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2.
近期研究发现了一类新的效应T细胞亚群，其可产生白细胞介素（IL）-17，被称为辅助性T细胞17（Th17）细胞，该细胞参与炎症性疾病的病理生理过程，并且被认为在发育上与调节性T（Treg）细胞相关。鉴于IL-2对Treg细胞的重要性，我们研究了IL-2在Th17细胞生成中的作用，并证明IL-2功能中一个此前未被认识到的方面是抑制IL-17的产生。IL-2的基因缺失或抗体阻断促进了Th17细胞亚群的分化。虽然信号转导和转录激活因子3（STAT3）似乎是维甲酸相关孤核受体γt（RORγt）和IL-17表达的关键正向调节因子，但IL-2的缺失或通过缺失转录因子信号转导和转录激活因子5（STAT5）破坏其信号传导会导致Th17细胞发育增强。我们得出结论，除了促进淋巴细胞激活诱导的细胞死亡以及Treg细胞的生成外，抑制Th17细胞极化似乎是IL-2的一项重要功能。
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