Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: implications for Th cell lineage commitment and maintenance

The Journal of Immunology : Official Journal of the American Association of Immunologists
Charles E EgwuaguIgal Gery

Abstract

Positive regulatory factors induced by IL-12/STAT4 and IL-4/STAT6 signaling during T cell development contribute to polarized patterns of cytokine expression manifested by differentiated Th cells. These two critical and antagonistic signaling pathways are under negative feedback regulation by a multimember family of intracellular proteins called suppressor of cytokine signaling (SOCS). However, it is not known whether these negative regulatory factors also modulate Th1/Th2 lineage commitment and maintenance. We show here that CD4(+) naive T cells constitutively express low levels of SOCS1, SOCS2, and SOCS3 mRNAs. These mRNAs and their proteins increase significantly in nonpolarized Th cells after activation by TCR signaling. We further show that differentiation into Th1 or Th2 phenotype is accompanied by preferential expression of distinct SOCS mRNA transcripts and proteins. SOCS1 expression is 5-fold higher in Th1 than in Th2 cells, whereas Th2 cells contain 23-fold higher levels of SOCS3. We also demonstrate that IL-12-induced STAT4 activation is inhibited in Th2 cells that express high levels of SOCS3 whereas IL-4/STAT6 signaling is constitutively activated in Th2 cells, but not Th1 cells, with high SOCS1 expression. These r...Continue Reading

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Citations

Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
Apr 12, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meifen ZhangIgal Gery
Jul 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas WernerPeter J Nelson
Jun 5, 2003·The Journal of Biological Chemistry·Cheng-Rong YuCharles E Egwuagu
Jul 9, 2003·Nature Medicine·Yoh-ichi SekiMasato Kubo
Nov 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Riikka LundRiitta Lahesmaa
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Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen CanfieldPaul Rothman
Feb 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Norbert KienzleAnne Kelso
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jason M ZimmererWilliam E Carson
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Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sharon H JacksonCharles E Egwuagu
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