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      Immunity

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          Abstract

          House dust mite-derived proteases contribute to allergic disorders in part by disrupting epithelial barrier function. Interleukin-33 (IL-33), produced by lung cells after exposure to protease allergens, can induce innate-type airway eosinophilia by activating natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2), to secrete Th2 type-cytokines. Because IL-33 also can induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are thought to cooperate with NH cells in enhancing protease or IL-33-mediated innate-type airway eosinophilia. However, we found that MC-deficient Kit(W-sh/W-sh) mice exhibited exacerbated protease-induced lung inflammation associated with reduced numbers of regulatory T (Treg) cells. Moreover, IL-2 produced by IL-33-stimulated MCs promoted expansion of numbers of Treg cells, thereby suppressing development of papain- or IL-33-induced airway eosinophilia. We have thus identified a unique anti-inflammatory pathway that can limit induction of innate-type allergic airway inflammation mediated by NH cells.

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          Author and article information

          Journal
          Immunity
          Immunity
          1097-4180
          1074-7613
          Jul 21 2015
          : 43
          : 1
          Affiliations
          [1 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan; Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos 7270, Switzerland.
          [2 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Immunology, Faculty of Health Science, Kyorin University, Tokyo, 192-8508, Japan.
          [3 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
          [4 ] Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan.
          [5 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Immune Regulation, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
          [6 ] Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
          [7 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
          [8 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of Molecular Immunology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
          [9 ] Department of Ophthalmology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
          [10 ] Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
          [11 ] Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
          [12 ] Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
          [13 ] MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK.
          [14 ] Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan.
          [15 ] Department of Immune Regulation, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan.
          [16 ] Department of Molecular Immunology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
          [17 ] Laboratory for Immune Cell System, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama 332-0012, Japan.
          [18 ] Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos 7270, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos 7270, Switzerland.
          [19 ] Departments of Pathology and of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
          [20 ] Laboratory for Immune Cell System, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan.
          [21 ] Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan; Division of Molecular Pathology, Research Institute for Biological Sciences, Tokyo University of Sciences, Chiba 278-0022, Japan.
          [22 ] Animal Research Center, Tokyo Medical University, Tokyo 160-8402, Japan.
          [23 ] Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama 332-0012, Japan. Electronic address: snakae@ims.u-tokyo.ac.jp.
          Article
          S1074-7613(15)00265-4 NIHMS707377
          10.1016/j.immuni.2015.06.021
          26200013
          c009b450-a8a7-4df4-9235-9a2de85bcea9
          Copyright © 2015 Elsevier Inc. All rights reserved.
          History

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