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Shibuya Lab
Research Project

We have identified paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptor (MAIR)-I and MAIR-II, whose extracellular domains are highly conserved with each other. By screening a macrophage cDNA library and the mouse genome, we and another group found that MAIR-I and MAIR-II are members of a multigene family consisting of at least 9 genes on a small segment of mouse chromosome 11 and now recognized as a CD300 family. Murine CD300 family genes are most similar to the human CMRF (CD300) family, which is located on human chromosome 17, syntenic region of mouse chromosome 11.  
    Emerging evidence suggests the CD300 family plays an important role in innate immunity. MAIR-I (assigned to be CD300a), contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic domain, and mediates inhibitory signals. We found phosphatidylserine (PS) exposed on apoptotic cells is a functional ligand for CD300a.We demonstrated that epithelial apoptotic cells negatively regulate commensal-mediated signal in dendritic cells via CD300a on dendritic cells for Treg cell proliferation and involved in colitis, bronchial asthma and atopic dermatitis. Also, CD300a on peritoneal mast cells and apoptotic cell association regulates neutrophil recruitment during sepsis and CD300a on inflammatory monocytes regulates Th2 cell responses. On the other hand, MAIR-II is expressed on subsets of peritoneal macrophages and B cells and associates with DAP12 and FcRγ chain that mediates activating signals. We found that MAIR-II regulates integrin-mediating migration of inflammatory monocytes during sepsis. Thus, MAIR-I (CD300a) and MAIR-II are candidates for molecular targets for therapy in patients with inflammatory and allergic diseases.