Marked Induction of c-Maf Protein during Th17 Cell Differentiation and Its Implication in Memory Th Cell Development*
Marked Induction of c-Maf Protein during Th17 Cell Differentiation and Its Implication in Memory Th Cell Development*
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DOI：
10.1074/jbc.m111.218867
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发表时间：
2011-03
期刊：
影响因子：
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通讯作者：
Kojiro Sato;F. Miyoshi;K. Yokota;Y. Araki;Y. Asanuma;Y. Akiyama;K. Yoh;Satoru Takahashi;H. Abur
中科院分区：
文献类型：
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作者：
Kojiro Sato;F. Miyoshi;K. Yokota;Y. Araki;Y. Asanuma;Y. Akiyama;K. Yoh;Satoru Takahashi;H. Abur
直到最近，效应T辅助细胞(Th)一直被分为两个亚群，Th1和Th2细胞。自从产生IL-17的Th17细胞被发现以来，Th17细胞一直受到人们的关注，主要是因为它们参与了各种炎症性疾病的发病机制。我们结合因子分析进行了转录组分析，发现在Th17分化过程中c-Maf的表达水平显著升高，c-Maf被认为是Th2分化的重要因素。IL-23受体(IL-23R)是c-Maf的转录靶点之一，对Th17细胞具有重要作用。有趣的是，对c-Maf转基因Th细胞的分析表明，c-Maf的过表达并没有导致Th17早期分化的加速，而是导致了记忆表型细胞的扩张，特别是具有Th1和Th17特征的细胞。与对照组相比，野生型小鼠记忆Th细胞表达高水平的c-maf、IL-23R、IL-17和干扰素-γ；相反，MAF−/−记忆Th细胞表达这些分子的基因水平较低。因此，我们认为c-Maf在记忆性Th细胞，特别是记忆性Th17细胞和Th1细胞的发育中起重要作用。
Until recently, effector T helper (Th) cells have been classified into two subsets, Th1 and Th2 cells. Since the discovery of Th17 cells, which produce IL-17, much attention has been given to Th17 cells, mainly because they have been implicated in the pathogenesis of various inflammatory diseases. We have performed transcriptome analysis combined with factor analysis and revealed that the expression level of c-Maf, which is considered to be important for Th2 differentiation, increases significantly during the course of Th17 differentiation. The IL-23 receptor (IL-23R), which is important for Th17 cells, is among putative transcriptional targets of c-Maf. Interestingly, the analysis of c-Maf transgenic Th cells revealed that the overexpression of c-Maf did not lead to the acceleration of the early stage of Th17 differentiation but rather to the expansion of memory phenotype cells, particularly with Th1 and Th17 traits. Consistently, mouse wild-type memory Th cells expressed higher mRNA levels of c-Maf, IL-23R, IL-17, and IFN-γ than control cells; in contrast, Maf−/− memory Th cells expressed lower mRNA levels of those molecules. Thus, we propose that c-Maf is important for the development of memory Th cells, particularly memory Th17 cells and Th1 cells.