The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines

Immunity. 1999 Jun;10(6):745-51. doi: 10.1016/s1074-7613(00)80073-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytokines / physiology*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Immunoglobulin E / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / pharmacology
  • Interleukin-5 / genetics
  • Interleukin-5 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Promoter Regions, Genetic / physiology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-maf
  • Spleen / cytology
  • Spleen / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Cytokines
  • DNA-Binding Proteins
  • Interleukin-13
  • Interleukin-5
  • Maf protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • Transcription Factors
  • Interleukin-10
  • Interleukin-4
  • Immunoglobulin E