Abstract
Anaphylaxis is a life-threatening immediate hypersensitivity reaction triggered by antigen capture by immunoglobulin E (IgE) bound to the high-affinity IgE receptor (FcɛRI) 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 FcɛRI 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.
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Acknowledgements
We thank T. Honjo, H. Karasuyama and K. Mukai for discussions and S. Mitsuishi for secretarial assistance. Supported by the Ministry of Education, Science and Culture of Japan and the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation.
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K.H., S.S., A.F., H.T. and T.S. did experiments and analyzed data; S.S. and K.S. contributed to experimental design and data interpretation; S.T.-H. designed and did experiments, analyzed data and wrote the paper; and A.S. supervised the overall project and wrote the paper.
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A.F., H.T., T.S. and S.S. are an employees of Ono Pharmaceutical.
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Hitomi, K., Tahara-Hanaoka, S., Someya, S. et al. An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E–mediated immediate hypersensitivity reactions. Nat Immunol 11, 601–607 (2010). https://doi.org/10.1038/ni.1886
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DOI: https://doi.org/10.1038/ni.1886
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