Nature Immunology 7, 851 - 858 (2006)
Published online: 25 June 2006; | doi:10.1038/ni1355
The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and functionYisong Y Wan1, 4, Hongbo Chi1, 4, Min Xie2, Michael D Schneider2
& Richard A Flavell1, 31
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. 2
Center for Cardiovascular Development and Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. 3
Howard Hughes Medical Institute, New Haven, Connecticut 06520, USA. 4
These authors contributed equally to this work.
Correspondence should be addressed to Richard A Flavell richard.flavell@yale.edu 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- B and the kinase Jnk. In effector T cells, TAK1 was dispensable for T cell receptor–dependent NF-B 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.
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