IFN-γ suppresses STAT6 phosphorylation by inhibiting its recruitment to the IL-4 receptor

Zan Huang, Junping Xin, John Coleman, Hua Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Polarized Th1 cells show a stable phenotype: they become insensitive to DL-4 stimulation and lose the potential to produce IL-4. Previously, we reported that IFN-γ played a critical role in stabilizing Th1 phenotype. However, the mechanism by which IFN-γ stabilizes Th1 phenotype is not clear. In this study, we compared STAT6 phosphorylation in wild-type (WT) and IFN-γ receptor knockout (IFNGR-/-) Th1 cells. We found a striking diminution of STAT6 phosphorylation in differentiated WT Th1 cells, but not in differentiated IFNGR-/- Th1 cells. The impairment of STAT6 phosphorylation in differentiated WT Th1 cells was not due to a lack of IL-4R expression or phosphorylation. Jak1 and Jak3 expression and phosphorylation were comparable in both cell types. No differential expression of suppressor of cytokine signaling 1 (SOCS1), SOCS3, or SOCS5 was observed in the two cell types. In addition, Src homology 2-containing phosphatase mutation did not affect IL-4-induced STAT6 phosphorylation in differentiated Th1 cells derived from viable motheaten (meν/meν) mice. These results led us to focus on a novel mechanism. By using a pulldown assay, we observed that STAT6 in WT Th1 cells bound less effectively to the phosphorylated IL-4R/GST fusion protein than that in IFNGR-/- Th1 cells. Our results suggest that IFN-γ may suppress phosphorylation of STAT6 by inhibiting its recruitment to the IL-4R.

Original languageEnglish (US)
Pages (from-to)1332-1337
Number of pages6
JournalJournal of Immunology
Volume174
Issue number3
DOIs
StatePublished - Feb 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'IFN-γ suppresses STAT6 phosphorylation by inhibiting its recruitment to the IL-4 receptor'. Together they form a unique fingerprint.

Cite this