Abstract
CD47 is a broadly expressed membrane protein that interacts with the myeloid inhibitory immunoreceptor SIRPα (also termed CD172a or SHPS-1). SIRPα is the prototypic member of the SIRP paired receptor family of closely related SIRP proteins. Engagement of SIRPα by CD47 provides a downregulatory signal that inhibits host cell phagocytosis, and CD47 therefore functions as a "don't-eat-me" signal. Here, we discuss recent structural analysis of CD47-SIRPα interactions and implications of this for the function and evolution of SIRPα and paired receptors in general. Furthermore, we review the proposed roles of CD47-SIRPα interactions in phagocytosis, (auto)immunity, and host defense, as well as its potential significance as a therapeutic target in cancer and inflammation and for improving graft survival in xenotransplantation.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antigens, Differentiation / chemistry
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism*
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Autoimmune Diseases / drug therapy
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Autoimmune Diseases / etiology
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CD47 Antigen / chemistry
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CD47 Antigen / genetics
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CD47 Antigen / metabolism*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Hematologic Diseases / drug therapy
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Hematologic Diseases / etiology
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Humans
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Immunological Synapses / immunology
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Immunological Synapses / metabolism
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Molecular Targeted Therapy
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Multigene Family
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Neoplasms / drug therapy
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Neoplasms / etiology
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Phagocytosis / drug effects
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Phagocytosis / immunology
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Protein Binding / drug effects
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Receptors, Immunologic / chemistry
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Antigens, Differentiation
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CD47 Antigen
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Receptors, Immunologic
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SIRPA protein, human