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Pertussis toxin-induced inhibition of Wnt/β-catenin signaling in dendritic cells promotes an autoimmune response in experimental autoimmune uveitis.
- Source :
- Journal of Neuroinflammation; 2/4/2023, p1-16, 16p
- Publication Year :
- 2023
-
Abstract
- Background: Previous reports have indicated that disrupting the Wnt/β-catenin pathway in dendritic cells (DCs) may affect the progression of autoimmune inflammation; however, the factors and timing that regulate Wnt/β-catenin signaling have not been clearly understood. Methods: Experimental autoimmune uveitis (EAU) mice and Vogt–Koyanagi–Harada disease (VKH) patient samples were used to detect the expression of Wnt/β-catenin pathway genes. Western blot, real-time PCR, flow cytometry, and ELISA were performed to examine the expression of components of the Wnt/β-catenin pathway and inflammatory factors. DC-specific β-catenin knockout mice and 6-bromoindirubin-3′-oxime (BIO) administered mice were used to observe the effect of disrupting the Wnt pathway on EAU pathogenesis. Results: Wnt/β-catenin signaling was inhibited in DCs during the induction phase of EAU. The inhibition was mediated by pertussis toxin (PTX), which promoted DC maturation, in turn promoting pathogenic T cell proliferation and differentiation. In vivo experiments confirmed that deleting β-catenin in DCs enhanced EAU severity, and pre-injection of PTX advanced EAU onset. Administration of a Wnt activator (BIO) limited the effects of PTX, in turn ameliorating EAU. Conclusions: Our results demonstrate that PTX plays a key role as a virulence factor in initiating autoimmune inflammation via DCs by inhibiting Wnt/β-catenin signaling in EAU, and highlight the potential mechanism by which infection can trigger apparent autoimmunity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17422094
- Database :
- Complementary Index
- Journal :
- Journal of Neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 161691866
- Full Text :
- https://doi.org/10.1186/s12974-023-02707-y