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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IL-9 induces differentiation of T_H17 cells and enhances function of FoxP3~+ natural regulatory T cells
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IL-9 induces differentiation of T_H17 cells and enhances function of FoxP3~+ natural regulatory T cells

机译：IL-9诱导T_H17细胞分化并增强FoxP3〜+自然调节性T细胞的功能

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摘要

The development of T helper (T_H)17 and regulatory T (T_(reg)) cells is reciprocally regulated by cytokines. Transforming growth factor (TGF)-β alone induces FoxP3~+ T_(reg) cells, but together with IL-6 or IL-21 induces T_H17 cells. Here we demonstrate that IL-9 is a key molecule that affects differentiation of T_H17 cells and T_(reg) function. IL-9 predominantly produced by T_H17 cells, synergizes with TGF-β1 to differentiate naieve CD4~+ T cells into T_H17 cells, while IL-9 secretion by T_H17 cells is regulated by IL-23. Interestingly, IL-9 enhances the suppressive functions of FoxP3~+ CD4~+ T_(reg) cells in vitro, and absence of IL-9 signaling weakens the suppressive activity of nT_(regs) in vivo, leading to an increase in effector cells and worsening of experimental autoimmune encephalomyelitis. The mechanism of IL-9 effects on T_H17 and T_(regs) is through activation of STAT3 and STAT5 signaling. Our findings highlight a role of IL-9 as a regulator of pathogenic versus protective mechanisms of immune responses.
机译：T辅助（T_H）17和调节性T（T_（reg））细胞的发育受到细胞因子的相互调节。单独的转化生长因子（TGF）-β诱导FoxP3〜+ T_（reg）细胞，但与IL-6或IL-21一起诱导T_H17细胞。在这里，我们证明IL-9是影响T_H17细胞分化和T_（reg）功能的关键分子。 IL-9主要由T_H17细胞产生，与TGF-β1协同作用，将幼稚的CD4〜+ T细胞分化为T_H17细胞，而T_H17细胞分泌的IL-9受IL-23调节。有趣的是，IL-9在体外增强了FoxP3〜+ CD4〜+ T_（reg）细胞的抑制功能，而没有IL-9信号减弱了体内nT_（regs）的抑制活性，从而导致效应细胞的增加。和实验性自身免疫性脑脊髓炎的恶化。 IL-9对T_H17和T_（regs）影响的机制是通过激活STAT3和STAT5信号传导。我们的发现强调了IL-9作为致病性与免疫反应保护机制的调节剂的作用。

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  • 作者

    Wassim Elyaman; Elizabeth M. Bradshaw; Catherine Uyttenhove; Valerie Dardalhon; Amit Awasthi; Jaime lmitola; Estelle Bettelli; Mohamed Oukka; Jacques van Snick; Jean-Christophe Renauld; Vijay K. Kuchroo; Samia J. Khoury;

  • 作者单位

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite Catholique de Louvain, Brussels, Belgium;

    Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, Universite Catholique de Louvain, Brussels, Belgium;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    autoimmunity; regulatory cells; tolerance;

    机译：自身免疫调节细胞;公差;

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