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Transforming growth factor-β induces development of the T_H17 lineage

机译：转化生长因子-β诱导T_H17谱系的发育

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A new lineage of effector CD4~+ T cells characterized by production of interleukin (IL)-17, the T-helper-17 (T_H17) lineage, was recently described based on developmental and functional features distinct from those of classical T_H1 and T_H2 lineages. Like T_H1 and T_H2, T_H17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens, such as extracellular bacteria. Aberrant T_H17 responses have been implicated in a growing list of autoimmune disorders. T_H17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rβ1, that pairs with unique, inducible components, IL-23R and IL-12Rβ2, to confer receptor responsiveness. Here we identify transforming growth factor-β (TGF-β) as a cytokine critical for commitment to T_H17 development. TGF-β acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-β on naive T cells is antagonized by interferon-γ and IL-4, thus providing a mechanism for divergence of the T_H1, T_H2 and T_H17 lineages.
机译：最近基于与经典T_H1和T_H2谱系不同的发育和功能特征，描述了一种新的效应CD4〜+ T细胞谱系，其特征是产生白介素（IL）-17，即T-helper-17（T_H17）谱系。 。像T_H1和T_H2一样，T_H17细胞几乎可以进化为提供针对特定类别病原体（例如细胞外细菌）的适应性免疫。异常的T_H17反应与越来越多的自身免疫性疾病有关。 T_H17的发育与IL-23相关，IL-23是IL-12细胞因子家族成员，与IL-12共有一个共同的亚基IL-12p40（参考文献8）。 IL-23和IL-12受体还共享一个亚基IL-12Rβ1，该亚基与独特的可诱导成分IL-23R和IL-12Rβ2配对以赋予受体响应性。在这里，我们确定转化生长因子-β（TGF-β）是对T_H17发育承诺至关重要的细胞因子。 TGF-β起到上调IL-23R表达的作用，从而赋予对IL-23的响应性。尽管对于在体外和体内产生IL-17的T细胞的发育是必不可少的，但是IL-23对于宿主抵抗细菌病原体（鼠疫杆菌）的保护是必需的。 TGF-β对幼稚T细胞的作用被干扰素-γ和IL-4拮抗，从而提供了T_H1，T_H2和T_H17谱系发散的机制。

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