Gadd45beta is important for perpetuating cognate and inflammatory signals in T cells.
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.
Lu
Binfeng
B
Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, New Haven, Connecticut 06520-8011, USA.
Ferrandino
Anthony F
AF
Flavell
Richard A
RA
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation / Q000276:immunology; D048670:MAP Kinase Kinase 4; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D002352:Carrier Proteins; D016207:Cytokines; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016693:Receptors, Antigen, T-Cell, alpha-beta; D048051:p38 Mitogen-Activated Protein Kinases; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins