Luminal microbes promote monocyte-stem cell interactions across a healthy colonic epithelium

Skoczek, D. A., Walczysko, P., Horn, N., Parris, A., Clare, S., Williams, Mark and Sobolewski, A. (2014) Luminal microbes promote monocyte-stem cell interactions across a healthy colonic epithelium. Journal of Immunology, 193 (1). pp. 439-451. ISSN 0022-1767

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Abstract

The intestinal epithelium forms a vital barrier between luminal microbes and the underlying mucosal immune system. Epithelial barrier function is maintained by continuous renewal of the epithelium and is pivotal for gut homeostasis. Breaching of the barrier causes mobilization of immune cells to promote epithelial restitution. However, it is not known whether microbes at the luminal surface of a healthy epithelial barrier influence immune cell mobilization to modulate tissue homeostasis. Using a mouse colonic mucosal explant model, we demonstrate that close proximity of luminal microbes to a healthy, intact epithelium results in rapid mucus secretion and movement of Ly6C+7/4+ monocytes closer to epithelial stem cells. These early events are driven by the epithelial MyD88-signaling pathway and result in increased crypt cell proliferation and intestinal stem cell number. Over time, stem cell number and monocyte–crypt stem cell juxtapositioning return to homeostatic levels observed in vivo. We also demonstrate that reduced numbers of tissue Ly6C+ monocytes can suppress Lgr5EGFP+ stem cell expression in vivo and abrogate the response to luminal microbes ex vivo. The functional link between monocyte recruitment and increased crypt cell proliferation was further confirmed using a crypt–monocyte coculture model. This work demonstrates that the healthy gut epithelium mediates communication between luminal bacteria and monocytes, and monocytes can modulate crypt stem cell number and promote crypt cell proliferation to help maintain gut homeostasis.

Item Type:	Article
Additional Information:	Copyright © 2014 The Authors.
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences Faculty of Science > School of Pharmacy
UEA Research Groups:	Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Depositing User:	Pure Connector
Date Deposited:	25 Jul 2014 12:54
Last Modified:	04 Jul 2023 10:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/49693
DOI:	10.4049/jimmunol.1301497

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