Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2.
Precursor CD4+ T cells develop into effector Th1 and Th2 cells that play a central role in the immune response. We show that the JNK MAP kinase pathway is induced in Th1 but not in Th2 effector cells upon antigen stimulation. Further, the differentiation of precursor CD4+ T cells into effector Th1 but not Th2 cells is impaired in JNK2-deficient mice. The inability of IL-12 to differentiate JNK2-deficient CD4+ T cells fully into effector Th1 cells is caused by a defect in IFNgamma production during the early stages of differentiation. The addition of exogenous IFNgamma during differentiation restores IL-12-mediated Th1 polarization in the JNK2-deficient mice. The JNK MAP kinase signaling pathway, therefore, plays an important role in the balance of Th1 and Th2 immune responses.
Yang
D D
DD
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Conze
D
D
Whitmarsh
A J
AJ
Barrett
T
T
Davis
R J
RJ
Rincón
M
M
Flavell
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017931:DNA Primers; D018808:Transcription Factor AP-1; D007371:Interferon-gamma; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases