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J Immunol. 2020 Feb 15;204(4):753-762. doi: 10.4049/jimmunol.1900180. Epub 2020 Jan 3.

Allergin-1 Immunoreceptor Suppresses House Dust Mite-Induced Allergic Airway Inflammation.

Author information

1
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
2
Department of Internal Medicine, Faculty of Medicine, Tsukuba Advanced Research Alliance, R&D Center for Innovative Drug Discovery, Tsukuba, Ibaraki 305-8575, Japan.
3
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; tokothr@md.tsukuba.ac.jp ashibuya@md.tsukuba.ac.jp.
4
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, R&D Center for Innovative Drug Discovery, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
5
Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; and.
6
Research Center of Immunology, Tsukuba Institute, Ono Pharmaceutical Co., Ltd., Tsukuba, Ibaraki 300-4247, Japan.

Abstract

House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b+ DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow-chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1-deficient CD11b+ bone marrow-derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE2 production from CD11b+ BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.

PMID:
31900344
DOI:
10.4049/jimmunol.1900180

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