Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial Damage
The intestinal epithelial barrier plays a critical role in the mucosal immunity. However, it remains largely unknown how the epithelial barrier is maintained after damage. Here we show that growth factor FGF2 synergized with interleukin-17 (IL-17) to induce genes for repairing of damaged epithelium....
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Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2015-09, Vol.43 (3), p.488-501 |
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Sprache: | eng |
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Zusammenfassung: | The intestinal epithelial barrier plays a critical role in the mucosal immunity. However, it remains largely unknown how the epithelial barrier is maintained after damage. Here we show that growth factor FGF2 synergized with interleukin-17 (IL-17) to induce genes for repairing of damaged epithelium. FGF2 or IL-17 deficiency resulted in impaired epithelial proliferation, increased pro-inflammatory microbiota outgrowth, and consequently worse pathology in a DSS-induced colitis model. The dysregulated microbiota in the model induced transforming growth factor beta 1 (TGFβ1) expression, which in turn induced FGF2 expression mainly in regulatory T cells. Act1, an essential adaptor in IL-17 signaling, suppressed FGF2-induced ERK activation through binding to adaptor molecule GRB2 to interfere with its association with guanine nucleotide exchange factor SOS1. Act1 preferentially bound to IL-17 receptor complex, releasing its suppressive effect on FGF2 signaling. Thus, microbiota-driven FGF2 and IL-17 cooperate to repair the damaged intestinal epithelium through Act1-mediated direct signaling cross-talk.
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•FGF2 and IL-17 signaling are critical for gut homeostasis during colitis•Microbiota-driven TGFβ1 controls FGF2 production in Treg cells during colitis•FGF2 cooperates with IL-17 to promote repair of damaged intestinal epithelium•Act1 mediates the cooperation of FGF2 and IL-17 signaling in gut
It remains largely unknown how the damaged intestinal epithelium is repaired to rebuild intestinal homeostasis. Song and colleagues demonstrate that dysregulated microbiota triggers FGF2 production from Treg cells, and FGF2 in turn cooperates with Th17-derived IL-17 to promote repair of damaged intestinal epithelium through adaptor molecule Act1-mediated signaling cross-talk. |
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ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2015.06.024 |