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

A Neil Barclay, Timo K Van den Berg

Research output: Contribution to journalReview articleAcademicpeer-review

508 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)25-50
Number of pages26
JournalAnnual review of immunology
Publication statusPublished - 2014


  • Animals
  • Antigens, Differentiation/chemistry
  • Autoimmune Diseases/drug therapy
  • CD47 Antigen/chemistry
  • Dendritic Cells/immunology
  • Hematologic Diseases/drug therapy
  • Humans
  • Immunological Synapses/immunology
  • Molecular Targeted Therapy
  • Multigene Family
  • Neoplasms/drug therapy
  • Phagocytosis/drug effects
  • Protein Binding/drug effects
  • Receptors, Immunologic/chemistry
  • Signal Transduction
  • T-Lymphocytes/immunology

Cite this