Evidence map›Paper›PMID 32768386›Full record

ArticleImmunity2020

CD47 Ligation Repositions the Inhibitory Receptor SIRPA to Suppress Integrin Activation and Phagocytosis.

Meghan A Morrissey, Nadja Kern, Ronald D Vale

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

139 citing papers in PubMed, 228 citations in OpenAlex.

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79 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Meghan A MorrisseyDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94158, USA.
Nadja KernDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94158, USA.
Ronald D ValeDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: valer@janelia.hhmi.org.
Howard Hughes Medical Institute · US

Funding

STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Collaboration between Phosphatidylserine receptorsF32GM120990 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MORRISSEY, MEGHAN A · 2016 to 2019
$177k
Howard Hughes Medical InstituteNIGMS NIH HHS F32 GM120990NIGMS NIH HHS T32 GM008284
6 · The paper itself

Abstract

CD47 acts as a "don't eat me" signal that protects cells from phagocytosis by binding and activating its receptor SIPRA on macrophages. CD47 suppresses multiple different pro-engulfment "eat me" signals, including immunoglobulin G (IgG), complement, and calreticulin, on distinct target cells. This complexity has limited understanding of how the "don't eat me" signal is transduced biochemically. Here, we utilized a reconstituted system with a defined set of signals to interrogate the mechanism of SIRPA activation and its downstream targets. CD47 ligation altered SIRPA localization, positioning SIRPA for activation at the phagocytic synapse. At the phagocytic synapse, SIRPA inhibited integrin activation to limit macrophage spreading across the surface of the engulfment target. Chemical reactivation of integrin bypassed CD47-mediated inhibition and rescued engulfment, similar to the effect of a CD47 function-blocking antibody. Thus, the CD47-SIRPA axis suppresses phagocytosis by inhibiting inside-out activation of integrin signaling in the macrophage, with implications to cancer immunotherapy applications.

Indexed as

AnimalsCalreticulinCD47 AntigenCell LineComplement System ProteinsHEK293 CellsHumansImmunoglobulin GIntegrinsMacrophage ActivationMacrophagesMiceMice, Inbred C57BLPhagocytosisPhosphatidylserinesRAW 264.7 CellsCalreticulinCD47 AntigenCd47 protein, mouseComplement System ProteinsImmunoglobulin GIntegrinsPhosphatidylserinesReceptors, ImmunologicSirpa protein, mouseCD47checkpoint blockadeengulfmentFc Receptorimmunological synapseimmunotherapyintegrinMacrophagephagocytosisSIRPA

Identifiers

PMID32768386
PMCPMC7453839
OpenAlexW3048347902

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.