title: Interferon-γ constrains cytokine production of group 2 innate lymphoid cells.
abstract: Group 2 innate lymphoid cells (ILC2s) produce a significant amount of interleukin-5 (IL-5), which supports eosinophil responses in various tissues; they also produce IL-13, which induces mucus production and contributes to tissue repair or fibrosis. The ILC2s are activated by alarmins, such as IL-33 released from epithelia, macrophages and natural killer T (NKT) cells in response to infection and allergen exposure, leading to epithelial injury. We examined gene expression in lung ILC2s and found that ILC2s expressed Ifngr1, the receptor for interferon-γ (IFN-γ). Interferon-γ severely inhibited IL-5 and IL-13 production by lung and kidney ILC2s. To evaluate the effects in vivo, we used α-galactosylceramide (α-GalCer) to induce NKT cells to produce IL-33 and IFN-γ. Intraperitoneal injection of α-GalCer in mice induced NKT cell activation resulting in IL-5 and IL-13 production by ILC2s. Administration of anti-IFN-γ together with α-GalCer significantly enhanced the production of IL-5 and IL-13 by ILC2s in lung and kidney. Conversely, cytokine production from ILC2s was markedly suppressed after injection of exogenous IL-33 in Il33(-/-) mice pre-treated with α-GalCer. Hence, IFN-γ induced or already present in tissues can impact downstream pleiotropic functions mediated by ILC2s, such as inflammation and tissue repair.
authors.affiliation: Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors.forename: Fujimi
authors.initials: F
authors.lastname: Kudo
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikutani
authors.affiliation: Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Seki
authors.affiliation: Department of Gastroenterology, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otsubo
authors.affiliation: Department of Gastroenterology, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors.forename: Yuki I
authors.initials: YI
authors.lastname: Kawamura
authors.affiliation: Department of Gastroenterology, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Dohi
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Oshima
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.|Cooperative Major in Advanced Health Science, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.affiliation: Laboratory of Systems Biology, Centre for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Toyama, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Gastroenterology, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.|Toyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.affiliation: Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000172:deficiency / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D017471:Receptors, Interferon / Q000819:agonists / Q000235:genetics / Q000276:immunology; D000096743:Interferon gamma Receptor
chemical_list: D005699:Galactosylceramides; D007371:Interferon-gamma; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C506535:Il33 protein, mouse; C493154:alpha-galactosylceramide
keywords: T helper type 2 cytokines; group 2 innate lymphoid cells; interferon-γ; interleukin-13; interleukin-5