Inflammatory macrophages prevent colonic goblet and enteroendocrine cell differentiation through Notch signaling.

Autor:	Atanga R; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM., Romero AS; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM., Hernandez AJ; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM., Peralta-Herrera E; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM.; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences, Albuquerque, NM., Merkley SD; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM., In JG; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM.; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences, Albuquerque, NM., Castillo EF; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences, Albuquerque, NM.; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences, Albuquerque, NM.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 29. Date of Electronic Publication: 2023 Jun 29.
DOI:	10.1101/2023.06.29.547119
Abstrakt:	Inflammatory macrophages in the intestine are a key pathogenic factor driving inflammatory bowel disease (IBD). Here, we report the role of inflammatory macrophage-mediated notch signaling on secretory lineage differentiation in the intestinal epithelium. Utilizing IL-10-deficient ( Il10 -/- ) mice, a model of spontaneous colitis, we found an increase in Notch activity in the colonic epithelium as well as an increase in intestinal macrophages expressing Notch ligands, which are increased in macrophages upon inflammatory stimuli. Furthermore, a co-culture system of inflammatory macrophages and intestinal stem and proliferative cells during differentiation reduced goblet and enteroendocrine cells. This was recapitulated when utilizing a Notch agonist on human colonic organoids (colonoids). In summary, our findings indicate that inflammatory macrophages upregulate notch ligands that activate notch signaling in ISC via cell-cell interactions, which in turn inhibits secretory lineage differentiation in the gastrointestinal (GI) tract. Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
Databáze:	MEDLINE
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