CD14型
单核细胞
脂多糖
川地163
败血症
趋化因子
促炎细胞因子
生物
发病机制
作者
Oluwabunmi O. Olaloye,Peng Liu,Jessica Toothaker,Blake T McCourt,Collin C. McCourt,Jenny Xiao,Erica Prochaska,Spenser Shaffer,Lael Werner,Upmc Nicu Faculty,Jordan Gringauz,Misty Good,Jeff Goldsmith,Xiaojing An,Fujing Wang,Scott B. Snapper,Dror S. Shouval,Kong Chen,George C. Tseng,Liza Konnikova
摘要
Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes IL8, CXCL1, CXCL2, CXCL5 and had enrichment of gene sets in pathways involved in chemotaxis, migration, phagocytosis, and reactive oxygen species generation. In summary, we identify a novel subtype of inflammatory monocytes/Mϕ associated with NEC that should be further evaluated as a potential biomarker of surgical NEC and a target for the development of NEC-specific therapeutics.
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