Single-cell RNA sequencing of intestinal immune cells in neonatal necrotizing enterocolitis

• Published in: Pediatric surgery international Vol. 39; no. 1; p. 179
• Main Authors: Oshima, Kazuo, Hinoki, Akinari, Uchida, Hiroo, Tanaka, Yujiro, Okuno, Yusuke, Go, Yasuhiro, Shirota, Chiyoe, Tainaka, Takahisa, Sumida, Wataru, Yokota, Kazuki, Makita, Satoshi, Takimoto, Aitaro, Kano, Yoko, Sawa, Shinichiro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 11.04.2023; Springer Nature B.V
• Subjects: Dendritic cells; Enterocolitis, Necrotizing - pathology; Gastrointestinal diseases; Gene expression; Genomics; Humans; Immunology; Infant, Newborn; Inflammation; Intestines - pathology; Lymphocytes; Medicine; Medicine & Public Health; Mortality; Necrosis; Newborn babies; Original Article; Pathogenesis; Pediatric Surgery; Pediatrics; Physiology; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Science; Sequence Analysis, RNA; Signal Transduction; Surgery; Necrotizing enterocolitis; Single-cell sequencing; Gene expression; Intestinal immune cells
• ISSN: 1437-9813; 0179-0358; 1437-9813
• DOI: 10.1007/s00383-023-05461-7

Purpose Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. Methods Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines. Results In all four cases, major immune cells, such as T cells (15.1–47.7%), B cells (3.1–19.0%), monocytes (16.5–31.2%), macrophages (1.6–17.4%), dendritic cells (2.4–12.2%), and natural killer cells (7.5–12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells. Conclusion Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.