CD47 halts Ptpn6-deficient neutrophils from provoking lethal inflammation.
CD47 halts Ptpn6-deficient neutrophils from provoking lethal inflammation.
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DOI：
10.1126/sciadv.ade3942
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发表时间：
2023-01-06
期刊：
影响因子：
13.6
通讯作者：
Gurung, Prajwal
中科院分区：
文献类型：
--
作者：
Mazgaeen, Lalita;Yorek, Matthew;Saini, Saurabh;Vogel, Peter;Meyerholz, David K.;Kanneganti, Thirumala-Devi;Gurung, Prajwal
携带SHP1蛋白的小鼠（以下简称Ptpn6spin小鼠）会发展为脚垫发炎的自身炎症性疾病。SHP1蛋白是由酪氨酸-208残基替换为天冬酰胺的单一氨基酸。研究CD47在Ptpn6spin小鼠中的功能的遗传杂交培育了Ptpn6spin × CD47−/−小鼠，这些小鼠没有按照预期的孟德尔比例出生。Ptpn6spin骨髓细胞被转移到经致命照射的cd47缺陷小鼠体内后，引起了显著的体重减轻和随后的死亡。在细胞水平上，ptpn6缺陷中性粒细胞促进了Cd47 - / -受体的体重减轻和死亡。我们假设，在接受Ptpn6spin细胞的Cd47 - / -小鼠中，肠道微生物群的泄漏促进了发病率和死亡率。病变Cd47−/−小鼠结肠细胞死亡和肠漏显著增加。最后，使用阿那白蛋白阻断IL-1可挽救患病Cd47−/−小鼠的发病率和死亡率。这些数据共同证明了CD47在调节Ptpn6spin小鼠致病性中性粒细胞中的保护作用。耐辐射CD47阻止ptpn6缺陷中性粒细胞引发小鼠致命疾病。
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. Radioresistant CD47 impedes Ptpn6-deficient neutrophils from provoking a fatal disease in mice.
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