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Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell–IL-22 axis

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  • aad9903_ArticleContent_ v3

    Rights statement: This is the author's version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Journal Title VOL 351 ISSUE 627, 4th Feb 2016, doi: 10.1126/science.aad9903

    Accepted author manuscript, 87 KB, Word document

Original languageEnglish
Pages (from-to)1333-1338
Number of pages6
JournalScience
Volume351
Issue number6279
DOIs
Publication statusPublished - 18 Mar 2016

Abstract

Systemic inflammation, resulting from massive release of pro-inflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are incompletely understood. We observed that prostaglandin E2 (PGE2) through its receptor EP4 is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treating with EP4 agonists. Mechanistically, we demonstrate that PGE2–EP4 signaling directly acts on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC/IL-22 axis impairs PGE2–mediated inhibition of systemic inflammation. Hence, PGE2–EP4 signaling inhibits systemic inflammation through ILC/IL-22 axis–dependent protection of gut barrier dysfunction.

    Research areas

  • NONSTEROIDAL ANTIINFLAMMATORY DRUGS, SEVERE SEPSIS, SEPTIC SHOCK, BARRIER, CELLS, INTERLEUKIN-22, PANCREATITIS, MULTICENTER, MORTALITY, INFECTION

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