Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility.

Abstract

BACKGROUND AND AIMS:

The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.

METHODS:

We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.

RESULTS:

Our results show that loss of myeloid PDGFR-α increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-α-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-α and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-α-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.

CONCLUSIONS:

Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.

• Authors: Ronja Dörk, Penelope Pelczar, Ahmad M Shiri, Annika Volmari, Elisabeth Zierz, Anastasios Giannou, Marius Böttcher, Lidia Bosurgi, Samuel Huber, Carolin F Manthey
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 17 Issue 11 Pg. 1858-1869 (Nov 24 2023) ISSN: 1876-4479 [Electronic] England
• PMID: 37377226 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Anti-Inflammatory Agents
• Dextran Sulfate

Topics

• Mice
• Animals
• Gastrointestinal Microbiome
• Colitis (pathology)
• Inflammatory Bowel Diseases (complications)
• Myeloid Cells (pathology)
• Anti-Inflammatory Agents (adverse effects)
• Dextran Sulfate
• Disease Models, Animal
• Mice, Inbred C57BL