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CD47 halts Ptpn6 -deficient neutrophils from provoking lethal inflammation
- Source :
- Science Advances. 9
- Publication Year :
- 2023
- Publisher :
- American Association for the Advancement of Science (AAAS), 2023.
-
Abstract
- Mice with SHP1 proteins, which have a single amino acid substitution from tyrosine-208 residue to asparagine (hereafter Ptpn6 spin mice), develop an autoinflammatory disease with inflamed footpads. Genetic crosses to study CD47 function in Ptpn6 spin mice bred Ptpn6 spin × Cd47 −/− mice that were not born at the expected Mendelian ratio. Ptpn6 spin 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 Ptpn6 spin 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 Ptpn6 spin mice.
- Subjects :
- Multidisciplinary
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi...........b57c5a852094a74aa7bcbed837f37c20