In:
Science, American Association for the Advancement of Science (AAAS), Vol. 351, No. 6279 ( 2016-03-18), p. 1333-1338
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 E 2 (PGE 2 ), through its receptor EP4, is down-regulated in human systemic inflammatory disease. Mice with reduced PGE 2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treatment with EP4 agonists. Mechanistically, we demonstrate that PGE 2 -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 PGE 2 -mediated inhibition of systemic inflammation. Hence, the ILC–IL-22 axis is essential in protecting against gut barrier dysfunction, enabling PGE 2 -EP4 signaling to impede systemic inflammation.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.aad9903
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2016
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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