Wan Yisong Y, Chi Hongbo, Xie Min, Schneider Michael D, Flavell Richard A
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nat Immunol. 2006 Aug;7(8):851-8. doi: 10.1038/ni1355. Epub 2006 Jun 25.
The kinase TAK1 is critical for innate and B cell immunity. The function of TAK1 in T cells is unclear, however. We show here that T cell-specific deletion of the gene encoding TAK1 resulted in reduced development of thymocytes, especially of regulatory T cells expressing the transcription factor Foxp3. In mature thymocytes, TAK1 was required for interleukin 7-mediated survival and T cell receptor-dependent activation of transcription factor NF-kappaB and the kinase Jnk. In effector T cells, TAK1 was dispensable for T cell receptor-dependent NF-kappaB activation and cytokine production, but was important for proliferation and activation of the kinase p38 in response to interleukins 2, 7 and 15. Thus, TAK1 is essential for the integration of T cell receptor and cytokine signals to regulate the development, survival and function of T cells.
激酶TAK1对天然免疫和B细胞免疫至关重要。然而，TAK1在T细胞中的功能尚不清楚。我们在此表明，T细胞特异性缺失编码TAK1的基因会导致胸腺细胞发育减少，尤其是表达转录因子Foxp3的调节性T细胞。在成熟胸腺细胞中，TAK1是白细胞介素7介导的存活以及转录因子NF-κB和激酶Jnk的T细胞受体依赖性激活所必需的。在效应T细胞中，TAK1对于T细胞受体依赖性NF-κB激活和细胞因子产生并非必需，但对于响应白细胞介素2、7和15时激酶p38的增殖和激活很重要。因此，TAK1对于整合T细胞受体和细胞因子信号以调节T细胞的发育、存活和功能至关重要。
