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Int Immunol. 2019 Dec 3. pii: dxz075. doi: 10.1093/intimm/dxz075. [Epub ahead of print]

Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice.

Author information

1
Ph.D. Program in Human Biology, School of Integrative and Global Majors.
2
Department of Immunology, Faculty of Medicine.
3
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), and R&D Center for Innovative Drug Discovery, University of Tsukuba, Tsukuba, Ibaraki, Japan.
4
Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima, Bunkyo-ku, Tokyo, Japan.
5
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, Japan.
6
Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Tsurumi-ku, Yokohama, Kanagawa, Japan.
7
Research Center of Immunology, Tsukuba Institute, ONO Pharmaceutical Company, Ltd, Tsukuba, Ibaraki, Japan.

Abstract

Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcεRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1-/-) mice developed more severe hypothermia, a higher mortality rate and a greater incidence of diarrhea than did wild-type (WT) mice in an oral ovalbumin (OVA)-induced food allergy model. MC-deficient Mas-TRECK mice, which had been reconstituted with either WT or Milr1-/- bone marrow-derived cultured MCs, did not develop hypothermia in this food allergy model. On the other hand, depletion of basophils by injection of anti-CD200R3 antibody rescued Milr1-/- mice from lethal hypothermia but not from diarrhea. In vitro analyses demonstrated that Allergin-1 inhibits IgE-dependent activation of both human and mouse basophils. Thus, Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis.

KEYWORDS:

diarrhea; food allergy; mast cells

PMID:
31793637
DOI:
10.1093/intimm/dxz075

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