The development of inflammatory TH-17 cells requires interferon-regulatory factor 4
The development of inflammatory TH-17 cells requires interferon-regulatory factor 4
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DOI：
10.1038/ni1500
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发表时间：
2007-09-01
影响因子：
30.5
通讯作者：
Lohoff, Michael
中科院分区：
文献类型：
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作者：
Bruestle, Anne;Heink, Sylvia;Lohoff, Michael
干扰素调节因子4（IRF 4）对辅助性T细胞2型的发育至关重要。在这里，我们表明，IRF 4也是产生白细胞介素17的T辅助细胞（T-H-17细胞），这是与实验性自身免疫性脑脊髓炎的关键。IRF 4缺陷（Irf 4（-/-））小鼠不会出现实验性自身免疫性脑脊髓炎，并且此类小鼠的辅助性T细胞未能分化为TH-17细胞。将野生型T辅助细胞转移到Irf 4（-/-）小鼠中使小鼠易患实验性自身免疫性脑脊髓炎。Irf 4（-/-）T辅助细胞ROR γ t表达较少，Foxp 3表达较多，这两种转录因子分别对T-H-17和调节性T细胞的分化很重要。这两种转录因子的调节改变有助于Irf 4（-/-）T辅助细胞的表型。我们的数据将IRF 4定位于T辅助细胞发育的中心，不仅影响T辅助细胞2型，而且影响T-H-17分化。
Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17-producing T helper cells (T-H-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4(-/-)) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into T-H-17 cells. Transfer of wild-type T helper cells into Irf4(-/-) mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4(-/-) T helper cells had less expression of ROR gamma t and more expression of Foxp3, transcription factors important for the differentiation of T-H-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4(-/-) T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also T-H-17 differentiation.