Prostaglandin E<sub>2</sub> promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33579710.
- Also identified by DOI 10.1126/sciadv.abd7954 and PMC identifier 7880593.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (T<sub>regs</sub>), yet how the microbiota-T<sub>reg</sub> cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), a well-known mediator of inflammation, inhibits mucosal T<sub>regs</sub> in a manner depending on the gut microbiota. PGE<sub>2</sub> through its receptor EP4 diminishes T<sub>reg</sub>-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE<sub>2</sub>-EP4 signaling modulates mucosal T<sub>reg</sub> responses and exacerbates intestinal inflammation. Mechanistically, PGE<sub>2</sub>-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE<sub>2</sub>-dependent T<sub>reg</sub> inhibition. Together, our findings provide emergent evidence that PGE<sub>2</sub>-mediated disruption of microbiota-T<sub>reg</sub> communication fosters intestinal inflammation.
Medical subject headings
- Gastrointestinal Microbiome
- T-Lymphocytes, Regulatory