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Mucosal Immunol. 2019 Mar;12(2):503-517. doi: 10.1038/s41385-018-0123-3. Epub 2019 Jan 7.

The recruitment of extra-intestinal cells to the injured mucosa promotes healing in radiation enteritis and chemical colitis in a mouse parabiosis model.

Author information

1
Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
2
Division of Pediatric Surgery, Johns Hopkins Children's Center and Department of Surgery, Baltimore, MD, USA.
3
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
5
Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. dhackam1@jhmi.edu.
6
Division of Pediatric Surgery, Johns Hopkins Children's Center and Department of Surgery, Baltimore, MD, USA. dhackam1@jhmi.edu.

Abstract

Mucosal healing occurs through migration and proliferation of cells within injured epithelium, yet these processes may be inadequate for mucosal healing after significant injury where the mucosa is denuded. We hypothesize that extra-intestinal cells can contribute to mucosal healing after injury to the small and large intestine. We generated parabiotic pairs between wild-type and tdTomato mice, which were then subjected to radiation-induced enteritis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. We now show that as compared with singleton mice, mice with a parabiotic partner were protected against intestinal damage as revealed by significantly reduced weight loss, reduced expression of pro-inflammatory cytokines, reduced enterocyte apoptosis, and improved crypt proliferation. Donor cells expressed CD45-, Sca-1+, c-kit+, and CXCR4+ and accumulated around the injured crypts but did not transdifferentiate into epithelia, suggesting that extra-intestinal cells play a paracrine role in the healing response, while parabiotic pairings with Rag1-/- mice showed improved healing, indicating that adaptive immune cells were dispensable for mucosal healing. Strikingly, ablation of the bone marrow of the donor parabionts removed the protective effects. These findings reveal that the recruitment of extra-intestinal, bone marrow-derived cells into the injured intestinal mucosa can promote mucosal healing, suggesting novel therapeutic approaches for severe intestinal disease.

PMID:
30617302
PMCID:
PMC6445662
DOI:
10.1038/s41385-018-0123-3
[Indexed for MEDLINE]
Free PMC Article

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