The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function.
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.
Wan
Yisong Y
YY
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Chi
Hongbo
H
Xie
Min
M
Schneider
Michael D
MD
Flavell
Richard A
RA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000276:immunology / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D000099151:MAP Kinase Kinase Kinase 7
D048670:MAP Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D018121:Receptors, Cytokine; D000099151:MAP Kinase Kinase Kinase 7