Lck mediates Th2 differentiation through effects on T-bet and GATA-3.
Lck mediates Th2 differentiation through effects on T-bet and GATA-3.
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LCK通过对T-BET和GATA-3的影响介导Th2的分化。
DOI：
10.4049/jimmunol.0901282
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发表时间：
2010-04-15
期刊：
影响因子：
--
通讯作者：
Stein PL
中科院分区：
文献类型：
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作者：
Kemp KL;Levin SD;Bryce PJ;Stein PL
Src家族激酶Lck已被证明在T细胞信号传导和发育中至关重要。然而，其在Th效应子功能中的作用还不清楚。Lck以前已被证明在Th 2细胞的细胞因子表达中起作用，但Lck影响Th 2效应功能的机制尚不清楚。使用小鼠模型，我们报告说，Lck是重要的调节IL-4在Th 2偏斜细胞的表达，但不是必要的Th 2细胞因子IL-5，IL-10，IL-13的表达。此外，在不存在Lck的情况下，T-bet和加塔-3的表达是异常的。此外，T-bet和加塔-3的这种非典型表达模式与Ifng基因座处组蛋白3乙酰化的增加和Th 1细胞因子IFN-γ的产生相关。我们发现加塔-3的过表达恢复了lck−/− Th 2细胞中IL-4的表达;这表明IL-4表达的降低部分是由于加塔-3的量减少。总之，这些数据暗示Lck通过对T-bet和加塔-3的作用介导Th 2分化。
The Src family kinase Lck has been shown to be crucial in T cell signaling and development. However, its role in Th effector functions is not well understood. Lck has previously been shown to play a role in the cytokine expression of Th2 cells, but the mechanism by which Lck influences Th2 effector functions is unknown. Using a mouse model, we report that Lck is important in regulating the expression of IL-4 in Th2 skewed cells but is not as necessary for the expression of Th2 cytokines IL-5, IL-10, and IL-13. Furthermore, in the absence of Lck, T-bet and GATA-3 expression is aberrant. Moreover, this atypical expression pattern of T-bet and GATA-3 correlates with increased histone 3 acetylation at the Ifng locus and production of the Th1 cytokine IFN-γ. We find overexpression of GATA-3 restores IL-4 expression in lck−/− Th2 cells; this indicates that the decreased IL-4 expression is due in part to reduced amounts of GATA-3. Taken together, these data imply that Lck mediates Th2 differentiation through effects on T-bet and GATA-3.