Hideaki Morita1, Terufumi Kubo2, Beate Rückert3, Avinash Ravindran4, Michael B Soyka5, Arturo Ottavio Rinaldi3, Kazunari Sugita2, Marcin Wawrzyniak2, Paulina Wawrzyniak2, Kenichiro Motomura6, Masato Tamari6, Keisuke Orimo6, Naoko Okada6, Ken Arae7, Kyoko Saito6, Can Altunbulakli2, Francesc Castro-Giner8, Ge Tan8, Avidan Neumann3, Katsuko Sudo9, Liam O'Mahony10, Kenya Honda11, Susumu Nakae12, Hirohisa Saito6, Jenny Mjösberg13, Gunnar Nilsson4, Kenji Matsumoto6, Mübeccel Akdis2, Cezmi A Akdis14. 1. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: morita-hi@ncchd.go.jp. 2. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland. 3. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. 4. Immunology and Allergy, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 5. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich and University of Zurich, Zurich, Switzerland. 6. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. 7. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; Department of Immunology, Faculty of Health Science, Kyorin University, Tokyo, Japan. 8. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland. 9. Animal Research Center, Tokyo Medical University, Tokyo, Japan. 10. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Department of Medicine and Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland. 11. Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; RIKEN Center for Integrative Medical Science (IMS), Kanagawa, Japan. 12. Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan. 13. Center for Infectious Medicine, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. 14. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland. Electronic address: akdisac@siaf.uzh.ch.
Abstract
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized. OBJECTIVE: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs). METHODS: IL-10+ ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite- or saline-treated mice. RESULTS: RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10+ ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell-like signature with expression of IL-10, cytotoxic T lymphocyte-associated protein 4, and CD25, with downregulated effector type 2-related markers, such as chemoattractant receptor-homologous molecule on TH2 cells and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite-treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro. CONCLUSION: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized. OBJECTIVE: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs). METHODS:IL-10+ ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite- or saline-treated mice. RESULTS:RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10+ ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell-like signature with expression of IL-10, cytotoxic T lymphocyte-associated protein 4, and CD25, with downregulated effector type 2-related markers, such as chemoattractant receptor-homologous molecule on TH2 cells and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite-treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro. CONCLUSION: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.
Authors: Matthew A Budd; Mahdis Monajemi; Sarah J Colpitts; Sarah Q Crome; C Bruce Verchere; Megan K Levings Journal: Diabetologia Date: 2021-09-22 Impact factor: 10.122
Authors: Mette D Hazenberg; Nienke J E Haverkate; Yannouck F van Lier; Hergen Spits; Lisette Krabbendam; Willem A Bemelman; Christianne J Buskens; Bianca Blom; Medya M Shikhagaie Journal: Blood Adv Date: 2019-11-26