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

Annu Rev Immunol. 2014:32:25-50. doi: 10.1146/annurev-immunol-032713-120142. Epub 2013 Nov 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

  • Antigens, Differentiation
  • CD47 Antigen
  • Receptors, Immunologic
  • SIRPA protein, human