CSF1 is expressed by the intestinal epithelial cells to regulate Mφ macrophages and maintain epithelial homeostasis and is downregulated in neonates with necrotizing enterocolitis.

Autor: Sun X; The Affiliated Hospital of Guiyang Medical University, Guiyang, 550004, China. Sam-sunxu@foxmail.com., Xu L; Children's Hospital of Soochow University, Suzhou, 215025, China., Ma S; Children's Hospital of Soochow University, Suzhou, 215025, China., Du J; The Affiliated Hospital of Guiyang Medical University, Guiyang, 550004, China., Gu H; The Affiliated Hospital of Guiyang Medical University, Guiyang, 550004, China., Wang J; Children's Hospital of Soochow University, Suzhou, 215025, China. wangjianszu@126.com.
Jazyk: angličtina
Zdroj: BMC pediatrics [BMC Pediatr] 2024 Sep 28; Vol. 24 (1), pp. 608. Date of Electronic Publication: 2024 Sep 28.
DOI: 10.1186/s12887-024-05047-9
Abstrakt: Background: Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R + macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R + macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates.
Methods: In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients.
Results: CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R + macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect.
Conclusions: Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R + macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction.
(© 2024. The Author(s).)
Databáze: MEDLINE
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