Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora.

TitleGroup 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora.
Publication TypeJournal Article
Year of Publication2013
AuthorsQiu J, Guo X, Chen Z-ME, He L, Sonnenberg GF, Artis D, Fu Y-X, Zhou L
JournalImmunity
Volume39
Issue2
Pagination386-99
Date Published2013 Aug 22
ISSN1097-4180
KeywordsAnimals, Cell Differentiation, Colitis, Interleukin-17, Interleukins, Intestines, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Receptor Subfamily 1, Group F, Member 3, Receptors, Aryl Hydrocarbon, Signal Transduction, Th17 Cells
Abstract

Aryl hydrocarbon receptor (Ahr) is crucial for the maintenance and function of group 3 innate lymphoid cells (ILCs), which are important in gut immunity. Because Ahr promotes T helper 17 (Th17) cell differentiation in vitro, it is reasonable to expect that Ahr would enhance Th17 cells in vivo. Instead, we show that Ahr deficiency caused increased intestinal Th17 cells, raising the possibility that group 3 ILCs could negatively regulate Th17 cells. Reduced innate interleukin-22 (IL-22) in Ahr-deficient mice allowed expansion of commensal segmented filamentous bacteria (SFB), known to promote Th17 cells. Compared to Rorc(+/+)Ahr(-/-) mice, Rorc(gfp/+)Ahr(-/-) mice had further reduced group 3 ILCs and were prone to spontaneous colitis with increased SFB and Th17 cells. Innate expression of Ahr played a protective role in T-cell-mediated experimental colitis by suppressing pathogenic Th17 cells. Our data reveal an intricate balance between ILCs and Th17 cells regulated by Ahr and commensal flora.

DOI10.1016/j.immuni.2013.08.002
Alternate JournalImmunity
PubMed ID23954130
PubMed Central IDPMC3884586
Grant ListAI089954 / AI / NIAID NIH HHS / United States
AI091962 / AI / NIAID NIH HHS / United States
CA134563 / CA / NCI NIH HHS / United States
CA141975 / CA / NCI NIH HHS / United States
P30 CA060553 / CA / NCI NIH HHS / United States
R01 AI089954 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
R21 AI091962 / AI / NIAID NIH HHS / United States

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