The Journal of Experimental Medicine
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Published 21 July 2003. doi:10.1084/jem.20021825
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© Rockefeller University Press, 0022-1007/2003/7/223 $5.00
The Journal of Experimental Medicine, Volume 198, Number 2, 223-233

Paired Activating and Inhibitory Immunoglobulin-like Receptors, MAIR-I and MAIR-II, Regulate Mast Cell and Macrophage Activation

Katsumi Yotsumoto1,2, Yasushi Okoshi1,2, Kazuko Shibuya1,2, Satoshi Yamazaki1,2,3, Satoko Tahara-Hanaoka1,2,3, Shin-ichiro Honda1,2,3, Mitsujiro Osawa1, Asato Kuroiwa5, Yoichi Matsuda5, Daniel G. Tenen6, Atsushi Iwama1,6, Hiromitsu Nakauchi1,4 and Akira Shibuya1,2,3

1 Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
2 Laboratory for Immune Receptor, RIKEN Research Center for Allergy and Immunology, Tsukuba, Ibaraki 305-0034, Japan
3 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Tsukuba, Ibaraki 305-8575, Japan
4 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tsukuba, Ibaraki 305-8575, Japan
5 Laboratory of Cytogenetics, Division of Bioscience, Graduate School of Environmental Earth Science and Chromosome Research Unit, Faculty of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan
6 Harvard Institute of Medicine, Harvard Medical School, Boston, MA 02115

Address correspondence to Akira Shibuya, Laboratory for Immune Receptor, RIKEN Research Center for Allergy and Immunology, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan. Phone: 81-29-836-9174; Fax: 81-29-836-9175; E-mail: ashibuya{at}md.tsukuba.ac.jp

Immune responses are regulated by opposing positive and negative signals triggered by the interaction of activating and inhibitory cell surface receptors with their ligands. Here, we describe novel paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptor (MAIR) I and MAIR-II, whose extracellular domains are highly conserved by each other. MAIR-I, expressed on the majority of myeloid cells, including macrophages, granulocytes, mast cells, and dendritic cells, contains the tyrosine-based sorting motif and the immunoreceptor tyrosine-based inhibitory motif-like sequences in the cytoplasmic domain and mediates endocytosis of the receptor and inhibition of IgE-mediated degranulation from mast cells. On the other hand, MAIR-II, expressed on subsets of peritoneal macrophages and B cells, associates with the immunoreceptor tyrosine-based activation motif-bearing adaptor DAP12 and stimulates proinflammatory cytokines and chemokine secretions from macrophages. Thus, MAIR-I and MAIR-II play important regulatory roles in cell signaling and immune responses.

Key Words: ITAM • ITIM • innate immunity • DAP12 • myeloid cells


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