An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions

Kaori Hitomi; Satoko Tahara-Hanaoka; Satoru Someya; Akira Fujiki; Hideaki Tada; Tetsuya Sugiyama; Shiro Shibayama; Kazuko Shibuya; Akira Shibuya

doi:10.1038/ni.1886

An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions

Nat Immunol. 2010 Jul;11(7):601-7. doi: 10.1038/ni.1886. Epub 2010 Jun 6.

Authors

Kaori Hitomi¹, Satoko Tahara-Hanaoka, Satoru Someya, Akira Fujiki, Hideaki Tada, Tetsuya Sugiyama, Shiro Shibayama, Kazuko Shibuya, Akira Shibuya

Affiliation

¹ Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.

PMID: 20526344
DOI: 10.1038/ni.1886

Abstract

Anaphylaxis is a life-threatening immediate hypersensitivity reaction triggered by antigen capture by immunoglobulin E (IgE) bound to the high-affinity IgE receptor (FcvarepsilonRI) on mast cells. However, the regulatory mechanism of mast cell activation is not completely understood. Here we identify an immunoglobulin-like receptor, Allergin-1, that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain, and show it was preferentially expressed on mast cells. Mouse Allergin-1 recruited the tyrosine phosphatases SHP-1 and SHP-2 and the inositol phosphatase SHIP. Coligation of Allergin-1 and FcvarepsilonRI suppressed IgE-mediated degranulation of bone marrow-derived cultured mast cells. Moreover, mice deficient in Allergin-1 developed enhanced passive systemic and cutaneous anaphylaxis. Thus, Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Bone Marrow Cells / pathology
Cell Degranulation*
Cells, Cultured
Humans
Hypersensitivity, Immediate / genetics
Hypersensitivity, Immediate / immunology*
Hypersensitivity, Immediate / metabolism
Immunoglobulin E / metabolism
Inositol Polyphosphate 5-Phosphatases
Mast Cells / immunology
Mast Cells / metabolism*
Mast Cells / pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Passive Cutaneous Anaphylaxis / immunology*
Phosphoric Monoester Hydrolases / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
Receptor Aggregation / immunology
Receptors, IgE / metabolism
Receptors, Immunologic / chemistry
Receptors, Immunologic / genetics
Receptors, Immunologic / immunology
Receptors, Immunologic / metabolism*

Substances

Milr1 protein, mouse
Receptors, IgE
Receptors, Immunologic
Immunoglobulin E
Phosphoric Monoester Hydrolases
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Inositol Polyphosphate 5-Phosphatases

Associated data

GENBANK/AB542950
GENBANK/AB542951
GENBANK/AB542952
GENBANK/AB542953