title: ICOS regulates the pool of group 2 innate lymphoid cells under homeostatic and inflammatory conditions in mice.
abstract: Group 2 innate lymphoid cells (ILC2s) are innate effectors playing an important role in the defense against helminthic infections and in the pathogenesis of allergic inflammation. Cytokines have been identified as the major stimuli driving ILC2 activation and expansion. Conversely, it is unclear whether costimulatory molecules contribute to regulation of ILC2 functions. ILC2s display high expression of inducible T-cell costimulator (ICOS), which belongs to the CD28 superfamily, and which has been shown to control late effector T-cell functions, and is of utmost importance for the humoral immune response. However, the biological function of ICOS expression on ILC2s is unknown. Here, we show that ICOS signaling in mice regulates ILC2 homeostasis independently of T cells and B cells, by promoting proliferation and accumulation of mature ILC2s in lung and intestine. In a model of IL-33-induced airway inflammation, ICOS controls ILC2 activation and eosinophil infiltration in the lung. Our data identify a role of ICOS in innate immunity and indicate that not only cytokines, but also costimulatory pathways such as those involving ICOS, can contribute to regulate the ILC2 pool. Thus, ICOS costimulation blockade, which is currently under clinical evaluation for inhibiting the humoral immune response, could also target innate inflammatory circuits.
authors.affiliation: Innate Immunity, Deutsches Rheuma-Forschungszentrum, Leibniz-Gemeinschaft, Berlin, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Paclik
authors.affiliation: Innate Immunity, Deutsches Rheuma-Forschungszentrum, Leibniz-Gemeinschaft, Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Stehle
authors.affiliation: Chronic Immune Reactions, Deutsches Rheuma-Forschungszentrum, Leibniz-Gemeinschaft, Berlin, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Lahmann
authors.affiliation: Chronic Immune Reactions, Deutsches Rheuma-Forschungszentrum, Leibniz-Gemeinschaft, Berlin, Germany.|Molecular Immunology, Robert Koch Institute, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.affiliation: Innate Immunity, Deutsches Rheuma-Forschungszentrum, Leibniz-Gemeinschaft, Berlin, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
mesh_terms: D000818:Animals; D006706:Homeostasis / Q000276:immunology*; D056724:Immunity, Humoral / Q000502:physiology*; D007113:Immunity, Innate / Q000502:physiology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: C556694:Icos protein, mouse; C506535:Il33 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D000067596:Interleukin-33
keywords: GATA3; ICOS; IL-33; ILC2; Innate lymphoid cell