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

AN Barclay, TK Van den Berg - Annual review of immunology, 2014 - annualreviews.org
Annual review of immunology, 2014annualreviews.org
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 …
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.
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