The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target.

Journal article

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.

Authors: Barclay, N; Van den Berg, T

• Publisher: Annual Reviews Inc.
• Journal: Annual review of immunology
• Volume: 32
• Issue: 1
• Pages: 25-50
• Publication date: 2014-01-01
• DOI: 10.1146/annurev-immunol-032713-120142
• EISSN: 1545-3278
• ISSN: 0732-0582
• Language: English
• Keywords: Animals; Dendritic Cells; Signal Transduction; Phagocytosis; T-Lymphocytes; Multigene Family; Neoplasms; Molecular Targeted Therapy; Immunological Synapses; Autoimmune Diseases; Antigens, CD47; Antigens, Differentiation; Hematologic Diseases; Humans; Protein Binding; Receptors, Immunologic