CD47 halts Ptpn6 -deficient neutrophils from provoking lethal inflammation

Lalita Mazgaeen; Matthew Yorek; Saurabh Saini; Peter Vogel; David K Meyerholz; Thirumala-Devi Kanneganti; Prajwal Gurung

doi:10.1126/sciadv.ade3942

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CD47 halts Ptpn6 -deficient neutrophils from provoking lethal inflammation

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CD47 halts Ptpn6 -deficient neutrophils from provoking lethal inflammation

Lalita Mazgaeen, Matthew Yorek, Saurabh Saini, Peter Vogel, David K Meyerholz, Thirumala-Devi Kanneganti and Prajwal Gurung

Science advances, Vol.9(1), eade3942

01/06/2023

DOI: 10.1126/sciadv.ade3942

PMCID: PMC9821860

PMID: 36608128

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Abstract

Mice with SHP1 proteins, which have a single amino acid substitution from tyrosine-208 residue to asparagine (hereafter Ptpn6spin mice), develop an autoinflammatory disease with inflamed footpads. Genetic crosses to study CD47 function in Ptpn6spin mice bred Ptpn6spin × Cd47−/− mice that were not born at the expected Mendelian ratio. Ptpn6spin bone marrow cells, when transferred into lethally irradiated Cd47-deficient mice, caused marked weight loss and subsequent death. At a cellular level, Ptpn6-deficient neutrophils promoted weight loss and death of the lethally irradiated Cd47−/− recipients. We posited that leakage of gut microbiota promotes morbidity and mortality in Cd47−/− mice receiving Ptpn6spin cells. Colonic cell death and gut leakage were substantially increased in the diseased Cd47−/− mice. Last, IL-1 blockade using anakinra rescued the morbidity and mortality observed in the diseased Cd47−/− mice. These data together demonstrate a protective role for CD47 in tempering pathogenic neutrophils in the Ptpn6spin mice.

Details

Title: Subtitle: CD47 halts Ptpn6 -deficient neutrophils from provoking lethal inflammation
Creators: Lalita Mazgaeen - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242, USA
Matthew Yorek - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
Saurabh Saini - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
Peter Vogel - St. Jude Children's Research Hospital
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Prajwal Gurung - Center for Immunology and Immune-Based Disease, University of Iowa, Iowa City, IA 52241, USA
Resource Type: Journal article
Publication Details: Science advances, Vol.9(1), eade3942
DOI: 10.1126/sciadv.ade3942
PMID: 36608128
PMCID: PMC9821860
NLM abbreviation: Sci Adv
eISSN: 2375-2548
Language: English
Date published: 01/06/2023
Academic Unit: Infectious Diseases; Pathology; Internal Medicine
Record Identifier: 9984358159302771

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