title: Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.
abstract: Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful pathogens. Together with T cells, the various ILC3 subsets maintain the balance between homeostasis and immune activation. Through genetic mapping, we identified a previously uncharacterized subset of NCR(-) ILC3s in mice that transiently express Ncr1, demonstrating previously undescribed heterogeneity within the ILC3 population. In addition, we showed that sustained Notch signaling was required for the maintenance of the NCR(+) phenotype and that the cytokine transforming growth factor-β (TGF-β) impaired the development of NCR(+) ILC3s. Thus, the plasticity of ILC3s is regulated by the balance between the opposing effects of Notch and TGF-β signaling, maintaining homeostasis in the face of continual challenges.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, INSERM, U1104, CNRS UMR 7280, 13288 Marseille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Viant
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Lucille C
authors.initials: LC
authors.lastname: Rankin
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, INSERM, U1104, CNRS UMR 7280, 13288 Marseille, France.
authors.forename: Mathilde J H
authors.initials: MJ
authors.lastname: Girard-Madoux
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Cyril
authors.initials: C
authors.lastname: Seillet
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR 5286, Université Lyon 1, Centre Léon Bérard, 69373 Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bartholin
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, 69364 Lyon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Huntington
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, INSERM, U1104, CNRS UMR 7280, 13288 Marseille, France. Immunologie, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, 13385 Marseille, France. vivier@ciml.univ-mrs.fr belz@wehi.edu.au.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia. vivier@ciml.univ-mrs.fr belz@wehi.edu.au.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; D008024:Ligands; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1