IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell–iTreg cell balance

iT reg cells and T H 17 cells share developmental steps, but their cellular fate depends on environmental cues. Weaver and colleagues show that IL-1 signaling alters the STAT3-STAT5 balance to skew cellular differentiation towards T H 17 CD4 + T cells. Interleukin 17 (IL-17)-producing helper T cells...

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Veröffentlicht in:Nature immunology 2015-03, Vol.16 (3), p.286-295
Hauptverfasser: Basu, Rajatava, Whitley, Sarah K, Bhaumik, Suniti, Zindl, Carlene L, Schoeb, Trenton R, Benveniste, Etty N, Pear, Warren S, Hatton, Robin D, Weaver, Casey T
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Sprache:eng
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Zusammenfassung:iT reg cells and T H 17 cells share developmental steps, but their cellular fate depends on environmental cues. Weaver and colleagues show that IL-1 signaling alters the STAT3-STAT5 balance to skew cellular differentiation towards T H 17 CD4 + T cells. Interleukin 17 (IL-17)-producing helper T cells (T H 17 cells) and CD4 + inducible regulatory T cells (iT reg cells) emerge from an overlapping developmental program. In the intestines, the vitamin A metabolite retinoic acid (RA) is produced at steady state and acts as an important cofactor to induce iT reg cell development while potently inhibiting T H 17 cell development. Here we found that IL-1 was needed to fully override RA-mediated expression of the transcription factor Foxp3 and induce protective T H 17 cell responses. By repressing expression of the negative regulator SOCS3 dependent on the transcription factor NF-κB, IL-1 increased the amplitude and duration of phosphorylation of the transcription factor STAT3 induced by T H 17-polarizing cytokines, which led to an altered balance in the binding of STAT3 and STAT5 to shared consensus sequences in developing T cells. Thus, IL-1 signaling modulated STAT activation downstream of cytokine receptors differently to control the T H 17 cell–iT reg cell developmental fate.
ISSN:1529-2908
1529-2916
DOI:10.1038/ni.3099