The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines.
IL-4 promotes the differentiation of naive CD4+ T cells into IL-4-producing T helper 2 (Th2) cells. Previous work provided suggestive but not conclusive evidence that the transcription factor c-Maf directed the tissue-specific expression of IL-4. It was not known whether c-Maf controlled the transcription of other Th2 cytokine genes. To elucidate the role of c-Maf in vivo, we examined cytokine production in mice lacking c-Maf (c-maf(-/-)). CD4+ T cells and NK T cells from c-maf(-/-) mice were markedly deficient in IL-4 production. However, the mice produced normal levels of IL-13 and IgE, and, when differentiated in the presence of exogenous IL-4, c-maf(-/-) T cells produced approximately normal levels of other Th2 cytokines. We conclude that c-Maf has a critical and selective function in IL-4 gene transcription in vivo.
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115-6017, USA.
J I
JI
Kim
I C
IC
Ho
M J
MJ
Grusby
L H
LH
Glimcher
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D007073:Immunoglobulin E / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000494:pharmacology; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051257:Proto-Oncogene Proteins c-maf; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D015848:Interleukin-5; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D014157:Transcription Factors; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E