TY - JOUR
T1 - Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora
AU - Qiu, Ju
AU - Guo, Xiaohuan
AU - Chen, Zong ming E.
AU - He, Lei
AU - Sonnenberg, Gregory F.
AU - Artis, David
AU - Fu, Yang Xin
AU - Zhou, Liang
N1 - Funding Information:
We thank the entire L.Z. laboratory for their help and suggestions. We thank S. Swaminathan and C. Goolsby at Flow Cytometry Facility (Northwestern University) for cell-sorting support. We thank the Mouse Histology and Phenotyping Laboratory (Northwestern University) for their services and assistance. We also thank D. Scholtens for the statistical analysis. The work was supported by the National Institutes of Health (AI089954 and AI091962 to L.Z. and CA141975 and CA134563 to Y.-X.F.) and by a Cancer Research Institute Investigator Award (to L.Z.). L.Z. is a Pew Scholar in Biomedical Sciences, supported by the Pew Charitable Trusts.
PY - 2013/8/22
Y1 - 2013/8/22
N2 - 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 invitro, it is reasonable to expect that Ahr would enhance Th17 cells invivo. 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 Th17cells. Compared to Rorc+/+Ahr-/- mice, Rorcgfp/+Ahr-/- mice had further reduced group 3ILCs and were prone to spontaneous colitis with increased SFB and Th17 cells. Innate expression ofAhr 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.
AB - 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 invitro, it is reasonable to expect that Ahr would enhance Th17 cells invivo. 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 Th17cells. Compared to Rorc+/+Ahr-/- mice, Rorcgfp/+Ahr-/- mice had further reduced group 3ILCs and were prone to spontaneous colitis with increased SFB and Th17 cells. Innate expression ofAhr 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.
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U2 - 10.1016/j.immuni.2013.08.002
DO - 10.1016/j.immuni.2013.08.002
M3 - Article
C2 - 23954130
AN - SCOPUS:84882668842
SN - 1074-7613
VL - 39
SP - 386
EP - 399
JO - Immunity
JF - Immunity
IS - 2
ER -