GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells.
The p38 and JNK stress-activated MAPK signal transduction pathways are activated by T cell receptor (TCR) signaling and are required for IFN-gamma production by TH1 effector cells. Here, we show that the expression of GADD45gamma is induced during T cell activation and that the level of expression is higher in TH1 cells than in TH2 cells. TH1 cells from GADD45gamma(-/-) mice are severely compromised in their abilities to activate p38 and JNK in response to TCR signaling, produce much less IFN-gamma upon restimulation, and are deficient in activation-induced cell death (AICD). Additionally, GADD45gamma deficiencies caused reduced contact hypersensitivity in mice. Thus, GADD45gamma mediates activation of the p38 and JNK pathways and effector function of TH1 cells.
Lu
B
B
Section of Immunobiology and, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520, USA.
Yu
H
H
Chow
C
C
Li
B
B
Zheng
W
W
Davis
R J
RJ
Flavell
R A
RA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins
D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D007371:Interferon-gamma; D018664:Interleukin-12; D015847:Interleukin-4; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011506:Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins