Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1

Immunity. 2000 Dec;13(6):805-15. doi: 10.1016/s1074-7613(00)00078-9.

Abstract

Interleukin 6 (IL-6) is a cytokine produced by immune and nonimmune cells and exhibits functional pleiotropy and redundancy. IL-6 plays an important role in the differentiation of several cell types. Here, we describe a novel function of IL-6: the negative regulation of CD4+ Th1 cell differentiation. While IL-6-directed CD4+ Th2 differentiation is mediated by IL-4, inhibition of Th1 differentiation by IL-6 is independent of IL-4. IL-6 upregulates suppressor of cytokine signaling 1 (SOCS1) expression in activated CD4+ T cells, thereby interfering with signal transducer and activator of transcription 1 (STAT1) phosphorylation induced by interferon gamma (IFNgamma). Inhibition of IFNgamma receptor-mediated signals by IL-6 prevents autoregulation of IFNgamma gene expression by IFNgamma during CD4+ T cell activation, thereby preventing Th1 differentiation. Thus, IL-6 promotes CD4+ Th2 differentiation and inhibits Th1 differentiation by two independent molecular mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-4 / biosynthesis
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Mice
  • Receptors, Interferon / metabolism
  • Repressor Proteins*
  • STAT1 Transcription Factor
  • Signal Transduction*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Th1 Cells / cytology*
  • Th1 Cells / metabolism
  • Trans-Activators / metabolism
  • Up-Regulation

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Interleukin-6
  • Receptors, Interferon
  • Repressor Proteins
  • STAT1 Transcription Factor
  • Socs1 protein, mouse
  • Stat1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • interferon gamma receptor
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma