Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation
| Autor: | Emgård, Johanna, Kammoun, Hana, García-Cassani, Bethania, Chesné, Julie, Parigi, Sara, 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, Huber, Samuel, Ludewig, Burkhard, Peduto, Lucie, Villablanca, Eduardo, Veiga-Fernandes, Henrique, Pereira, Joao, Flavell, Richard, Willinger, Tim |
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| Přispěvatelé: | Karolinska Institutet [Stockholm], Champalimaud Centre for the Unknown [Lisbon], Stroma, inflammation et réparation tissulaire - Stroma, Inflammation and Tissue Repair, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Brustzentrum Kantonsspital St. Gallen, University of Manchester [Manchester], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Yale University School of Medicine, Howard Hughes Medical Institute (HHMI), This work was supported by a Sir Henry Dale Wellcome Trust Fellowship (105644/Z/14/Z) to M.R.H., NIH grant RO1AI113040 to J.P.P., Swiss National Science Foundation grant 159188 to B.L., and a Junior Investigator Research Grant from the Center for Innovative Medicine at the Karolinska Institutet and a grant from the Åke Wiberg Foundation to T.W., We thank A. Rongvaux, L. Evangelisti, J. Stein, C. Hughes, and L. Borelli for help with generating Gpr183−/− mice. We also thank L. Zenewicz for providing cDNA and G. Eberl (Pasteur Institute) for providing Rorc(γt)GFP transgenic mice. R.A.F. is an investigator of the Howard Hughes Medical Institute., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Yale School of Medicine [New Haven, Connecticut] (YSM), TOMASSO DEVERGE, Carina |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
GPR183
[SDV.IMM] Life Sciences [q-bio]/Immunology colon cell migration Colon innate lymphoid cells Fluorescent Antibody Technique Innate lymphoid cells Colitis Flow Cytometry Ligands Real-Time Polymerase Chain Reaction Article Receptors G-Protein-Coupled Mice Cell Movement inflammation Animals Cytokines oxysterols [SDV.IMM]Life Sciences [q-bio]/Immunology Lymphocytes lymphoid tissue EBI2 Signal Transduction |
| Zdroj: | Immunity Immunity, Elsevier, 2018, 48 (1), pp.120-132.e8. ⟨10.1016/j.immuni.2017.11.020⟩ Immunity, 2018, 48 (1), pp.120-132.e8. ⟨10.1016/j.immuni.2017.11.020⟩ Emgard, J, Kammoun, H, Garcia-Cassani, B, Chesne, J, Parigi, S M, Jacob, J-M, Cheng, H-W, Evren, E, Das, S, Czarnewski, P, Sleiers, N, Melo Gonzalez, F, Kvedaraite, E, Svensson, M, Scandella, E, Hepworth, M, Huber, S, Ludewig, B, Peduto, L, Villablanca, E J, Veiga-Fernandes, H, Pereira, J P, Flavell, R A & Willinger, T 2018, ' Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation ', Immunity, vol. 48, no. 1, pp. 120-132 . https://doi.org/10.1016/j.immuni.2017.11.020 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2017.11.020⟩ |
| Popis: | Summary 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. Graphical Abstract Highlights • ILC3s sense cholesterol metabolites (oxysterols) through the receptor GPR183 • GPR183 and its ligand 7α,25-OHC promote ILC3 migration to CPs and ILFs • GPR183 and 7α,25-OHC are critical for CP and ILF formation in the colon • GPR183 controls inflammatory tissue remodeling during immune-mediated colitis ILC3s maintain healthy organ function in the intestine, but how ILC3s directly detect environmental cues is poorly understood. Emgård et al. find that GPR183 and oxysterols control the localization and LTi function of ILC3s and thereby promote the formation of colonic lymphoid tissues in the steady state and inflammation. |
| Databáze: | OpenAIRE |
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