Down-regulation of IL-4 gene transcription and control of Th2 cell differentiation by a mechanism involving NFAT1

Immunity. 1997 Dec;7(6):849-60. doi: 10.1016/s1074-7613(00)80403-3.

Abstract

Transcription factors of the NFAT family play a critical role in the immune response by activating the expression of cytokines and other inducible genes in antigen-stimulated cells. Here we show that a member of this family, NFAT1, is involved in down-regulating the late phase of IL-4 gene transcription, thus inhibiting T helper 2 responses. Whereas stimulated T cells from wild-type mice show a transient increase and then a rapid decline in the steady-state levels of IL-4 mRNA in vitro, the levels of IL-4 gene transcripts in NFAT1-deficient T cells are maintained at high levels under the same conditions. Consistent with this observation, NFAT1-/- mice are more susceptible to infection with Leishmania major. This report provides evidence that NFAT proteins regulate not only the initiation but also the termination of gene transcription.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease Susceptibility
  • Down-Regulation*
  • Female
  • Gene Deletion
  • Interleukin-4 / genetics*
  • Leishmania major / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • RNA, Messenger
  • Spleen / cytology
  • T-Lymphocytes / cytology
  • Th2 Cells / cytology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Interleukin-4