Projects per year
Abstract / Description of output
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.
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 |
Keywords / Materials (for Non-textual outputs)
- NONSTEROIDAL ANTIINFLAMMATORY DRUGS
- SEVERE SEPSIS
- SEPTIC SHOCK
- BARRIER
- CELLS
- INTERLEUKIN-22
- PANCREATITIS
- MULTICENTER
- MORTALITY
- INFECTION
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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
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HIGH ACCURACY, LOW VOLUME HOST DIRECTED DETECTION OF NEONATAL SEPSIS
Ghazal, P. & Dickinson, P.
UK central government bodies/local authorities, health and hospital authorities
1/07/12 → 31/12/13
Project: Research
Profiles
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Rodger Duffin
- Deanery of Clinical Sciences - Personal Chair of Thoracic Toxicology
- Centre for Inflammation Research
Person: Academic: Research Active
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Damian Mole
- Deanery of Clinical Sciences - 1777 Chair of Surgery
- Edinburgh Imaging
- Centre for Inflammation Research
Person: Academic: Research Active
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Adriano Rossi
- Deanery of Clinical Sciences - Personal Chair of Respiratory & Inflammation Pharmacology
- Centre for Inflammation Research
Person: Academic: Research Active