Journal article 691 views 320 downloads
Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
Science Advances, Volume: 7, Issue: 7
Swansea University Author:
Luke Davies
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DOI (Published version): 10.1126/sciadv.abd7954
Abstract
The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2)...
Published in: | Science Advances |
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ISSN: | 2375-2548 |
Published: |
American Association for the Advancement of Science (AAAS)
2021
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Online Access: |
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URI: | https://cronfa.swan.ac.uk/Record/cronfa61695 |
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Abstract: |
The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2), a well-known mediator of inflammation, inhibits mucosal Tregs in a manner depending on the gut microbiota. PGE2 through its receptor EP4 diminishes Treg-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE2-EP4 signaling modulates mucosal Treg responses and exacerbates intestinal inflammation. Mechanistically, PGE2-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE2-dependent Treg inhibition. Together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation. |
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College: |
Faculty of Medicine, Health and Life Sciences |
Funders: |
Cancer Research UK; MRC UK |
Issue: |
7 |