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

Duffin, R. et al. (2016) Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science, 351(6279), pp. 1333-1338. (doi: 10.1126/science.aad9903) (PMID:26989254)

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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 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smyth, Dr Danielle and Maizels, Professor Rick
Authors: Duffin, R., O'Connor, R. A., Crittenden, S., Forster, T., Yu, C., Zheng, X., Smyth, D., Robb, C. T., Rossi, F., Skouras, C., Tang, S., Richards, J., Pellicoro, A., Weller, R. B., Breyer, R. M., Mole, D. J., Iredale, J. P., Anderton, S. M., Narumiya, S., Maizels, R.M., Ghazal, P., Howie, S. E., Rossi, A. G., and Yao, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Science
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
ISSN (Online):1095-9203
Published Online:18 March 2016

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