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Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

TitleAnti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.
Publication TypeJournal Article
Year of Publication2018
AuthorsChu C, Moriyama S, Li Z, Zhou L, Flamar A-L, Klose CSN, Moeller JB, Putzel GG, Withers DR, Sonnenberg GF, Artis D
JournalCell Rep
Volume23
Issue13
Pagination3750-3758
Date Published2018 Jun 26
ISSN2211-1247
Abstract

The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection.

DOI10.1016/j.celrep.2018.05.099
Alternate JournalCell Rep
PubMed ID29949760
PubMed Central IDPMC6209103
Grant ListR01 AI074878 / AI / NIAID NIH HHS / United States
R21 DK110262 / DK / NIDDK NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
P01 AI106697 / AI / NIAID NIH HHS / United States
R01 AI123368 / AI / NIAID NIH HHS / United States
DP5 OD012116 / OD / NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
/ / Wellcome Trust / United Kingdom
R21 AI083480 / AI / NIAID NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States
R01 AI061570 / AI / NIAID NIH HHS / United States
R01 AI097333 / AI / NIAID NIH HHS / United States