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