The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target.
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.
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK; email: neil.barclay@path.ox.ac.uk.
A Neil
AN
Barclay
Timo K
TK
Van den Berg
D000818:Animals; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000209:etiology; D051928:CD47 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006402:Hematologic Diseases / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D005810:Multigene Family; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000943:Antigens, Differentiation; D051928:CD47 Antigen; D011971:Receptors, Immunologic; C501920:SIRPA protein, human