Gadd45beta is important for perpetuating cognate and inflammatory signals in T cells

Nat Immunol. 2004 Jan;5(1):38-44. doi: 10.1038/ni1020. Epub 2003 Dec 14.


Gadd45beta (growth arrest and DNA damage-inducible, beta) is involved in cell cycle arrest, apoptosis, signal transduction and cell survival. In T cells, Gadd45b was rapidly induced by T cell receptor (TCR) and inflammatory signals. Deficiency of Gadd45beta in CD4+ T cells impaired their responses to TCR stimulation or inflammatory cytokines. ERK, p38 and JNK activation were all substantially suppressed in Gadd45beta-deficient CD4+ T cells. Cytokine production by Gadd45beta-deficient CD4+ T cells was also impaired. Furthermore, Gadd45beta mediated inflammatory cytokine production by dendritic cells, and Gadd45beta-deficient mice showed an impaired T helper type 1 response during Listeria monocytogenes infection. Gadd45beta is therefore a critical feedback regulator that perpetuates both cognate and inflammatory signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Enzyme Activation
  • Female
  • Immunity, Innate / immunology
  • JNK Mitogen-Activated Protein Kinases*
  • Lymphocyte Activation / immunology
  • MAP Kinase Kinase 4
  • Male
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases / immunology
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / immunology
  • Mitogen-Activated Protein Kinases / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Signal Transduction / immunology
  • Th1 Cells / immunology
  • p38 Mitogen-Activated Protein Kinases


  • Antigens, Differentiation
  • Carrier Proteins
  • Cytokines
  • Gadd45b protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases