Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation
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Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation. / Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim.
in: IMMUNITY, Jahrgang 48, Nr. 1, 16.01.2018, S. 120-132.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation
AU - Emgård, Johanna
AU - Kammoun, Hana
AU - García-Cassani, Bethania
AU - Chesné, Julie
AU - Parigi, Sara M
AU - Jacob, Jean-Marie
AU - Cheng, Hung-Wei
AU - Evren, Elza
AU - Das, Srustidhar
AU - Czarnewski, Paulo
AU - Sleiers, Natalie
AU - Melo-Gonzalez, Felipe
AU - Kvedaraite, Egle
AU - Svensson, Mattias
AU - Scandella, Elke
AU - Hepworth, Matthew R
AU - Huber, Samuel
AU - Ludewig, Burkhard
AU - Peduto, Lucie
AU - Villablanca, Eduardo J
AU - Veiga-Fernandes, Henrique
AU - Pereira, João P
AU - Flavell, Richard A
AU - Willinger, Tim
N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2018/1/16
Y1 - 2018/1/16
N2 - Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.
AB - Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.
KW - Animals
KW - Cell Movement
KW - Colitis
KW - Colon
KW - Cytokines
KW - Flow Cytometry
KW - Fluorescent Antibody Technique
KW - Ligands
KW - Lymphocytes
KW - Lymphoid Tissue
KW - Mice
KW - Oxysterols
KW - Real-Time Polymerase Chain Reaction
KW - Receptors, G-Protein-Coupled
KW - Signal Transduction
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.immuni.2017.11.020
DO - 10.1016/j.immuni.2017.11.020
M3 - SCORING: Journal article
C2 - 29343433
VL - 48
SP - 120
EP - 132
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 1
ER -