| First Author | Mazgaeen L | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 1 | Pages | eade3942 |
| PubMed ID | 36608128 | Mgi Jnum | J:332672 |
| Mgi Id | MGI:7428083 | Doi | 10.1126/sciadv.ade3942 |
| Citation | Mazgaeen L, et al. (2023) CD47 halts Ptpn6-deficient neutrophils from provoking lethal inflammation. Sci Adv 9(1):eade3942 |
| abstractText | 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) x 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. |
