TY - JOUR
T1 - CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants
AU - Olaloye, Oluwabunmi O.
AU - Liu, Peng
AU - Toothaker, Jessica M.
AU - McCourt, Blake T.
AU - McCourt, Collin C.
AU - Xiao, Jenny
AU - Prochaska, Erica
AU - Shaffer, Spenser
AU - Werner, Lael
AU - Gringauz, Jordan
AU - Good, Misty
AU - Goldsmith, Jeffrey D.
AU - An, Xiaojing
AU - Wang, Fujing
AU - Snapper, Scott B.
AU - Shouval, Dror
AU - Chen, Kong
AU - Tseng, George
AU - Konnikova, Liza
N1 - Funding Information:
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.
Funding Information:
This research was funded by the University of Pittsburgh, Yale School of Medicine, and Eunice Kennedy Shriver National Institute of Child Health and Human Development grant no. 1R21HD102565-01A1.
Publisher Copyright:
© 2021 Olaloye et al.
PY - 2021/7/16
Y1 - 2021/7/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85110603579&partnerID=8YFLogxK
U2 - 10.1084/jem.20200344
DO - 10.1084/jem.20200344
M3 - Article
C2 - 34269788
AN - SCOPUS:85110603579
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
M1 - e20200344
ER -