The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function

Nat Immunol. 2006 Aug;7(8):851-8. doi: 10.1038/ni1355. Epub 2006 Jun 25.

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-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Survival / immunology
  • Flow Cytometry
  • Immunoblotting
  • Lymphocyte Activation / immunology
  • MAP Kinase Kinase 4 / immunology
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Kinase Kinases / immunology*
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • Mice, Transgenic
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cytokine / immunology*
  • Receptors, Cytokine / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology

Substances

  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • Receptors, Cytokine
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • MAP Kinase Kinase 4