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 SIRP alpha (also termed CD172a or SHPS-1). SIRP alpha is the prototypic member of the SIRP paired receptor family of closely related SIRP proteins. Engagement of SIRP alpha 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-SIRP alpha interactions and implications of this for the function and evolution of SIRP alpha and paired receptors in general. Furthermore, we review the proposed roles of CD47-SIRP alpha 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.