The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4

Cell. 1996 Jun 28;85(7):973-83. doi: 10.1016/s0092-8674(00)81299-4.

Abstract

The molecular basis for the distinctive cytokine expression of CD4+ T helper 1 (Th1) and T helper 2 (Th2) subsets remains elusive. Here, we report that the proto-oncogene c-maf, a basic region/leucine zipper transcription factor, controls tissue-specific expression of IL-4. c-Maf is expressed in Th2 but not Th1 clones and is induced during normal precursor cell differentiation along a Th2 but not Th1 lineage. c-Maf binds to a c-Maf response element (MARE) in the proximal IL-4 promoter adjacent to a site footprinted by extracts from Th2 but not Th1 clones. Ectopic expression of c-Maf transactivates the IL-4 promoter in Th1 cells, B cells, and nonlymphoid cells, a function that maps to the MARE and Th2-specific footprint. Furthermore, c-Maf acts in synergy with the nuclear factor of activated T cells (NF-ATp) to initiate endogeneous IL-4 production by B cells. Manipulation of c-Maf may alter Th subset ratios in human disease.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / physiology
  • Base Sequence
  • Blotting, Northern
  • CD3 Complex / genetics
  • Cell Differentiation / genetics
  • Cells, Cultured / physiology
  • Chromosome Mapping
  • Clone Cells / physiology
  • Cytokines / genetics
  • DNA Footprinting
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation / physiology
  • Gene Library
  • Genetic Complementation Test
  • Interleukin-4 / genetics*
  • Lymphoma / genetics
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-maf
  • Recombinant Proteins / genetics
  • Repressor Proteins / genetics
  • Sensitivity and Specificity
  • Spleen / cytology
  • T-Lymphocytes, Helper-Inducer / physiology
  • Transcription, Genetic / genetics

Substances

  • CD3 Complex
  • Cytokines
  • DNA, Complementary
  • DNA-Binding Proteins
  • Maf protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • Recombinant Proteins
  • Repressor Proteins
  • Interleukin-4