Prostaglandin E 2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (T ), yet how the microbiota-T cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E (PGE ), a wel...
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Veröffentlicht in: | Science advances 2021-02, Vol.7 (7) |
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Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (T
), yet how the microbiota-T
cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E
(PGE
), a well-known mediator of inflammation, inhibits mucosal T
in a manner depending on the gut microbiota. PGE
through its receptor EP4 diminishes T
-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE
-EP4 signaling modulates mucosal T
responses and exacerbates intestinal inflammation. Mechanistically, PGE
-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE
-dependent T
inhibition. Together, our findings provide emergent evidence that PGE
-mediated disruption of microbiota-T
communication fosters intestinal inflammation. |
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ISSN: | 2375-2548 2375-2548 |
DOI: | 10.1126/sciadv.abd7954 |