Format

Send to

Choose Destination
Immunity. 2000 Dec;13(6):805-15.

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

Author information

1
Department of Medicine, University of Vermont, Burlington 05405, USA.

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.

PMID:
11163196
DOI:
10.1016/s1074-7613(00)00078-9
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center