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

A Neil Barclay; Timo K Van den Berg

doi:https://doi.org/10.1146/annurev-immunol-032713-120142

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 journal › Review article › Academic › peer-review

538 Citations (Scopus)

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.

Original language	English
Pages (from-to)	25-50
Number of pages	26
Journal	Annual review of immunology
Volume	32
DOIs	https://doi.org/10.1146/annurev-immunol-032713-120142
Publication status	Published - 2014

Keywords

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

Access to Document

https://doi.org/10.1146/annurev-immunol-032713-120142

Cite this

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

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. ",

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author = "Barclay, {A Neil} and {Van den Berg}, {Timo K}",

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doi = "https://doi.org/10.1146/annurev-immunol-032713-120142",

language = "English",

volume = "32",

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journal = "Annual review of immunology",

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T1 - The interaction between signal regulatory protein alpha (SIRPα) and CD47

T2 - structure, function, and therapeutic target

AU - Barclay, A Neil

AU - Van den Berg, Timo K

PY - 2014

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N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, Differentiation/chemistry

KW - Autoimmune Diseases/drug therapy

KW - CD47 Antigen/chemistry

KW - Dendritic Cells/immunology

KW - Hematologic Diseases/drug therapy

KW - Humans

KW - Immunological Synapses/immunology

KW - Molecular Targeted Therapy

KW - Multigene Family

KW - Neoplasms/drug therapy

KW - Phagocytosis/drug effects

KW - Protein Binding/drug effects

KW - Receptors, Immunologic/chemistry

KW - Signal Transduction

KW - T-Lymphocytes/immunology

U2 - https://doi.org/10.1146/annurev-immunol-032713-120142

DO - https://doi.org/10.1146/annurev-immunol-032713-120142

M3 - Review article

C2 - 24215318

SN - 0732-0582

VL - 32

SP - 25

EP - 50

JO - Annual review of immunology

JF - Annual review of immunology

ER -