Interferon‐γ constrains cytokine production of group 2 innate lymphoid cells |
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| Authors: | Fujimi Kudo Masashi Ikutani Yoichi Seki Takeshi Otsubo Yuki I Kawamura Taeko Dohi Kenshiro Oshima Masahira Hattori Susumu Nakae Kiyoshi Takatsu Satoshi Takaki |
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| Institution: | 1. Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan;2. Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan;3. Department of Gastroenterology, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan;4. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan;5. Cooperative Major in Advanced Health Science, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan;6. Laboratory of Systems Biology, Centre for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;7. Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Toyama, Japan;8. Toyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan |
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| 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. |
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| Keywords: | group 2 innate lymphoid cells interferon‐γ interleukin‐5 interleukin‐13 T helper type 2 cytokines |
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