STAT6 inhibits T-bet-independent Th1 cell differentiation.
STAT6 inhibits T-bet-independent Th1 cell differentiation.
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DOI：
10.1016/j.bbrc.2009.03.101
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发表时间：
2009-05
影响因子：
3.1
通讯作者：
T. Tamachi;H. Takatori;M. Fujiwara;K. Hirose;Y. Maezawa;S. Kagami;A. Suto;N. Watanabe;I. Iwamoto;H. Nakajima
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文献类型：
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作者：
T. Tamachi;H. Takatori;M. Fujiwara;K. Hirose;Y. Maezawa;S. Kagami;A. Suto;N. Watanabe;I. Iwamoto;H. Nakajima
STAT 6在Th 2细胞分化中起关键作用，而STAT 4和T-bet在Th 1细胞分化中起重要作用。然而，在Th 1/Th 2细胞分化过程中，这些转录因子的相互作用在很大程度上仍然是未知的。为了进一步研究Th 1/Th 2细胞分化的调控机制，我们产生了缺乏STAT 6和T-bet的小鼠（STAT 6 −/−T-bet−/−小鼠）。重要的是，尽管STAT 6 −/−T-bet−/−小鼠和STAT 6 −/−小鼠的Th 2细胞分化严重且类似地减少，但与T-bet−/−小鼠相比，STAT 6 −/−T-bet−/−小鼠的Th 1细胞分化部分得到拯救。虽然在STAT 6 −/−T-bet−/− CD 4 +T细胞和T-bet−/− CD 4 +T细胞之间没有观察到IL-12 R β2和STAT 4的表达的显著差异，但与T-bet −/− CD 4 + T细胞相比，IL-12诱导的STAT 6 −/−T-bet−/− CD 4 + T细胞中的STAT 4磷酸化增加。这些结果表明，STAT 6通过抑制IL-12-STAT 4信号传导抑制T-bet非依赖性Th 1细胞分化。
STAT6 plays critical roles in Th2 cell differentiation, whereas STAT4 and T-bet are important for Th1 cell differentiation. However, it is still largely unknown about the cross talk of these transcription factors during Th1/Th2 cell differentiation. To further address the regulatory mechanisms underlying Th1/Th2 cell differentiation, we generated the mice lacking both STAT6 and T-bet (STAT6−/−T-bet−/−mice). Importantly, although Th2 cell differentiation was severely and similarly decreased in STAT6−/−T-bet−/−mice and STAT6−/−mice, Th1 cell differentiation was rescued in part in STAT6−/−T-bet−/−mice as compared with that in T-bet−/−mice. While no significant difference was observed in the expression of IL-12Rβ2 and STAT4 between STAT6−/−T-bet−/−CD4+T cells and T-bet−/−CD4+T cells, IL-12-induced STAT4 phosphorylation was increased in STAT6−/−T-bet−/−CD4+T cells as compared with that in T-bet−/−CD4+T cells. These results indicate that STAT6 inhibits T-bet-independent Th1 cell differentiation by suppressing IL-12-STAT4 signaling.