Cited by 847Phagocytosis and Immune RegulationCell death mechanisms and regulationInflammasome and immune disorders

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The Interaction Between Signal Regulatory Protein Alpha (SIRPα) and CD47: Structure, Function, and Therapeutic Target

Barclay, A. Neil, van den Berg, Timo K.·2014·Annual Review of Immunology

DOI 10.1146/annurev-immunol-032713-120142

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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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Authors: Barclay, A. N., & van den Berg, T. K.
Affiliations: University of Oxford (GB)
Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands;
ORCID: Barclay, A. Neil
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2014-03-21
Volume: 32
Issue: 1
Pages: 25-50
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-032713-120142
OpenAlex: W2139418176
Cited by: 841
References: 155
Citations by year: 2026: 63 · 2025: 107 · 2024: 108 · 2023: 84 · 2022: 77 · 2021: 89 · 2020: 89 · 2019: 51 · 2018: 44 · 2017: 60 · 2016: 32 · 2015: 26 · 2014: 11
FWCI: 2.01
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords: CD47, SIRPα, don't eat me signal, phagocytosis, immune evasion, autoimmunity, host defense, cancer immunotherapy, inflammation, xenotransplantation, graft survival, receptor evolution
MeSH terms: Animals, Antigens, Differentiation, Autoimmune Diseases, Dendritic Cells, Multigene Family, Hematologic Diseases, Humans, Neoplasms, Phagocytosis, Protein Binding, Receptors, Immunologic, T-Lymphocytes, Signal Transduction, CD47 Antigen, Immunological Synapses, Molecular Targeted Therapy

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The Interaction Between Signal Regulatory Protein Alpha (SIRPα) and CD47: Structure, Function, and Therapeutic Target

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