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.
CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants
Disclosures: M. Good reported grants from National Institutes of Health, Takeda Pharmaceuticals, and Astarte Medical Partners, and personal fees from Abbott Laboratories outside the submitted work; in addition, M. Good had a patent to use interleukin-22 for the prevention or treatment of necrotizing enterocolitis pending (PCT/US2017/027806). S.B. Snapper reported grants from Pfizer, Amgen, Novartis, and Takeda, personal fees from Pfizer, Amgen, Lilly, BMS, Pandion, Merck, and Takeda, and other from Pandion outside the submitted work. No other disclosures were reported.
- Award Id(s): 1R21HD102565-01A1
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Oluwabunmi O. Olaloye, Peng Liu, Jessica M. Toothaker, Blake T. McCourt, Collin C. McCourt, Jenny Xiao, Erica Prochaska, Spenser Shaffer, Lael Werner, UPMC NICU Faculty, UPMC Pediatric Surgery Faculty, Jordan Gringauz, Misty Good, Jeffrey D. Goldsmith, Xiaojing An, Fujing Wang, Scott B. Snapper, Dror Shouval, Kong Chen, George Tseng, Liza Konnikova; CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants. J Exp Med 6 September 2021; 218 (9): e20200344. doi: https://doi.org/10.1084/jem.20200344
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