Abstract
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-κB and the kinase Jnk. In effector T cells, TAK1 was dispensable for T cell receptor–dependent NF-κB 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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Acknowledgements
We thank C.B. Wilson for CD4-Cre–transgenic mice, E. Eynon for discussions and F. Manzo for secretarial assistance. Supported by the National Institutes of Health (R.A.F.), the Howard Hughes Medical Institute (R.A.F.), the Cancer Research Institute (Y.Y.W.), the Arthritis National Research Foundation (H.C.) and the Charles H. Hood Foundation (H.C.).
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Supplementary information
Supplementary Fig. 1
Phenotypic analysis of DP and CD4 SP thymocytes. (PDF 98 kb)
Supplementary Fig. 2
Surface expression of IL-7Rα is not altered on TAK1 deficient cells. (PDF 24 kb)
Supplementary Fig. 3
TAK1 deficiency results in accelerated T cell apoptosis in the long-term culture. (PDF 34 kb)
Supplementary Fig. 4
TAK1-deficient effector T cells compete poorly with wild-type counterparts in response to cytokine stimulation. (PDF 378 kb)
Supplementary Fig. 5
The numbers of cells recovered at the end of [3H]thymidine incorporation are comparable between TAK1 intact and deficient effector T cells. (PDF 367 kb)
Supplementary Fig. 6
TAK1 deletion did not affect the expression of CD25, IL-7Rα or IL-15Rα on effector T cells. (PDF 29 kb)
Supplementary Fig. 7
TAK1 is essential for the constitutive p38 activity in thymocytes. (PDF 85 kb)
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Wan, Y., Chi, H., Xie, M. et al. The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function. Nat Immunol 7, 851–858 (2006). https://doi.org/10.1038/ni1355
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DOI: https://doi.org/10.1038/ni1355
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