Wdr63 Deletion Aggravates Ulcerative Colitis Likely by Affecting Th17/Treg Balance and Gut Microbiota
10.16476/j.pibb.2024.0148
- VernacularTitle:Wdr63缺失可能通过影响Th17/Treg平衡和肠道菌群来加重溃疡性结肠炎
- Author:
Hao ZHU
1
;
Meng-Yuan ZHU
1
;
Yang-Yang CAO
1
;
Qiu-Bo YANG
1
;
Zhi-Peng FAN
1
Author Information
1. Beijing Institute for Dental Research, Capital Medical University School of Stomatology, Beijing100050, China
- Publication Type:Journal Article
- Keywords:
Wdr63;
Th17/Treg;
ulcerative colitis;
inflammation;
immune;
microbiology
- From:
Progress in Biochemistry and Biophysics
2025;52(1):209-222
- CountryChina
- Language:English
-
Abstract:
ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
