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Abstract
Systemic
inflammation, which results from the massive release of proinflammatory
molecules into the circulatory system, is a major risk factor for
severe illness, but the precise mechanisms underlying its control are
not fully understood. We observed that prostaglandin ESystemic inflammation, which results from the massive release of
proinflammatory molecules into the circulatory system, is a major risk
factor for severe illness, but the precise mechanisms underlying its
control are not fully 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 treatment with EP4 agonists.
Mechanistically, we demonstrate that PGE2-EP4 signaling acts
directly 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, the ILC–IL-22 axis is
essential in protecting against gut barrier dysfunction, enabling PGE2-EP4 signaling to impede systemic inflammation.
Original language | English |
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Pages (from-to) | 1333-1338 |
Number of pages | 6 |
Journal | Science |
Volume | 351 |
Issue number | 6279 |
DOIs | |
Publication status | Published - 18 Mar 2016 |
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Dive into the research topics of 'Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis'. Together they form a unique fingerprint.Projects
- 1 Finished
Profiles
-
Professor Sir John P Iredale
- Bristol Medical School - Professor of Experimental Medicine
- Cancer
Person: Academic , Member