An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions.
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.
Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Kaori
K
Hitomi
Satoko
S
Tahara-Hanaoka
Satoru
S
Someya
Akira
A
Fujiki
Hideaki
H
Tada
Tetsuya
T
Sugiyama
Shiro
S
Shibayama
Kazuko
K
Shibuya
Akira
A
Shibuya
D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D015550:Cell Degranulation; D002478:Cells, Cultured; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D011940:Receptor Aggregation / Q000276:immunology; D017455:Receptors, IgE / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
C551887:Milr1 protein, mouse; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D007073:Immunoglobulin E; D010744:Phosphoric Monoester Hydrolases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D000072181:Inositol Polyphosphate 5-Phosphatases