The p38 mitogen-activated protein kinase regulates effector functions of primary human CD4 T cells.
The role of p38 mitogen-activated protein kinase in primary human T cells is incompletely understood. We analyzed in detail the role of p38 in the regulation of effector functions and differentiation of human CD4 T cells by using a p38-specific inhibitor and a dominant-negative mutant of p38. p38 was found to mediate expression of IL-10 and the Th2 cytokines IL-4, IL-5, and IL-13 in both, primary naive and memory T cells. In contrast, inhibition of p38 activity did not affect expression of the Th1 cytokines IFN-gamma and TNF induced by TCR-stimulation, but decreased IL-12-mediated IFN-gamma expression. Cytokine expression from established Th2 effector cells was also regulated by p38, however, the role of p38 was less pronounced compared to primary CD4 T cells. p38 MAPK regulated cytokine gene expression at both, the transcriptional level by activating gene transcription and the post-transcriptional level by stabilizing cytokine mRNA. As a result of the effect of p38 on IL-4 expression, p38 activity modulated differentiation of naive precursor T cells by inducing a shift of the Th1/Th2 balance toward the immuno-modulatory Th2 direction. Together, the data suggest that p38 plays a key role in human Th2 cell immune responses.
Dodeller
Francis
F
Nikolaus Fiebiger Center for Molecular Medicine, Clinical Research Group III, University of Erlangen-Nuremberg, Erlangen, Germany.
Skapenko
Alla
A
Kalden
Joachim R
JR
Lipsky
Peter E
PE
Schulze-Koops
Hendrik
H
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology; D018418:Th2 Cells / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases