| First Author | Zhang Z | Year | 2023 |
| Journal | J Neuroinflammation | Volume | 20 |
| Issue | 1 | Pages | 24 |
| PubMed ID | 36739434 | Mgi Jnum | J:339545 |
| Mgi Id | MGI:7433629 | Doi | 10.1186/s12974-023-02707-y |
| Citation | Zhang Z, et al. (2023) Pertussis toxin-induced inhibition of Wnt/beta-catenin signaling in dendritic cells promotes an autoimmune response in experimental autoimmune uveitis. J Neuroinflammation 20(1):24 |
| abstractText | BACKGROUND: Previous reports have indicated that disrupting the Wnt/beta-catenin pathway in dendritic cells (DCs) may affect the progression of autoimmune inflammation; however, the factors and timing that regulate Wnt/beta-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/beta-catenin pathway genes. Western blot, real-time PCR, flow cytometry, and ELISA were performed to examine the expression of components of the Wnt/beta-catenin pathway and inflammatory factors. DC-specific beta-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/beta-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 beta-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/beta-catenin signaling in EAU, and highlight the potential mechanism by which infection can trigger apparent autoimmunity. |
