Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
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DOI：
10.1038/ni1254
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发表时间：
2005-11-01
影响因子：
30.5
通讯作者：
Weaver, CT
中科院分区：
文献类型：
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作者：
Harrington, LE;Hatton, RD;Weaver, CT
产生白细胞介素17（IL-17）的CD 4（+）T细胞与自身免疫相关，尽管控制其发展的精确机制尚不清楚。在这里，我们提出的数据挑战了与T辅助细胞1型（T（H）1）或T（H）2谱系共享发育途径的想法，而是支持我们称之为“T-H-17”的独特效应谱系的想法。IFN-γ和IL-4可有效抑制幼稚前体细胞向T-H-17细胞的分化，而定型T-H-17细胞对T（H）1或T（H）2细胞因子的抑制具有抗性。在不存在IFN-γ和IL-4的情况下，IL-23诱导幼稚前体细胞分化为T-H-17细胞，而不依赖于转录因子STAT 1、T-bet、STAT 4和STAT 6。这些发现为理解IFN-γ信号传导的抑制如何增强可加剧自身免疫的致病性T-H-17效应细胞的发展提供了基础。
CD4(+) T cells producing interleukin 17 (IL-17) are associated with autoimmunity, although the precise mechanisms that control their development are undefined. Here we present data that challenge the idea of a shared developmental pathway with T helper type 1 (T(H)1) or T(H)2 lineages and instead favor the idea of a distinct effector lineage we call 'T-H-17'. The development of T-H-17 cells from naive precursor cells was potently inhibited by interferon-gamma (IFN-gamma) and IL-4, whereas committed T-H-17 cells were resistant to suppression by T(H)1 or T(H)2 cytokines. In the absence of IFN-gamma and IL-4, IL-23 induced naive precursor cells to differentiate into T-H-17 cells independently of the transcription factors STAT1, T-bet, STAT4 and STAT6. These findings provide a basis for understanding how inhibition of IFN-gamma signaling enhances development of pathogenic T-H-17 effector cells that can exacerbate autoimmunity.