Batten Marcel, Li Ji, Yi Sothy, Kljavin Noelyn M, Danilenko Dimitry M, Lucas Sophie, Lee James, de Sauvage Frederic J, Ghilardi Nico
Department of Molecular Biology, Genentech, South San Francisco, California 94080, USA.
Nat Immunol. 2006 Sep;7(9):929-36. doi: 10.1038/ni1375. Epub 2006 Aug 13.
Interleukin 27 (IL-27) was first characterized as a proinflammatory cytokine with T helper type 1-inducing activity. However, subsequent work has demonstrated that mice deficient in IL-27 receptor (IL-27R alpha) show exacerbated inflammatory responses to a variety of challenges, suggesting that IL-27 has important immunoregulatory functions in vivo. Here we demonstrate that IL-27R alpha-deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis and generated more IL-17-producing T helper cells. IL-27 acted directly on effector T cells to suppress the development of IL-17-producing T helper cells mediated by IL-6 and transforming growth factor-beta. This suppressive activity was dependent on the transcription factor STAT1 and was independent of interferon-gamma. Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation.
白细胞介素27（IL-27）最初被鉴定为一种具有诱导1型辅助性T细胞活性的促炎细胞因子。然而，随后的研究表明，缺乏白细胞介素27受体（IL-27Rα）的小鼠对各种刺激表现出加剧的炎症反应，这表明IL-27在体内具有重要的免疫调节功能。在此，我们证明IL-27Rα缺陷小鼠对实验性自身免疫性脑脊髓炎高度敏感，并产生更多产生白细胞介素17的辅助性T细胞。IL-27直接作用于效应T细胞，以抑制由白细胞介素6和转化生长因子-β介导的产生白细胞介素17的辅助性T细胞的发育。这种抑制活性依赖于转录因子信号转导和转录激活因子1（STAT1），且独立于干扰素-γ。最后，IL-27抑制白细胞介素6介导的T细胞增殖。这些数据为在几种体内炎症模型中观察到的IL-27介导的免疫抑制提供了一种机制解释。
