Transcriptomic profiling of iris tissue highlights the role of CXCL13 in developing Vogt-Koyanagi-Harada disease
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Purpose
To investigate the molecular pathological changes and immunopathogenic mechanisms underlying the development of intraocular inflammation in Vogt-Koyanagi-Harada (VKH) disease.
Methods
The mRNA-seq, bioinformatics analysis, and molecular biology experiments were performed. Experimental autoimmune uveitis (EAU) model was established in both wild-type and CXCL13-knockout mice.
Results
Compared with healthy controls, a total of 3522 differentially expressed genes (DEGs) were identified in the iris of the VKH group. GO and KEGG enrichment analysis showed that upregulated DEGs were predominantly enriched in the biological processes related to immune/inflammation pathways and immune cell activation. PPI analysis on DEGs revealed that the B-cell chemokine CXCL13 was the top-ranked hub gene. RT-qPCR results indicated a remarkably elevated mRNA expression level of CXCL13 in the iris of patients with VKH or Behcet's uveitis (BU), with a more pronounced increase in the VKH group. Consistently, the concentration of CXCL13 in the aqueous humor of VKH and BU patients was significantly increased, and was higher in the VKH patients. In the EAU mouse model, CXCL13 knockout led to a significant attenuation of intraocular inflammation. Additionally, a reduction in the proportions of Th1/Th17 cells and the secretion of IFN-γ/IL-17A was observed, accompanied by an increase in the proportion of Treg cells and the secretion of IL-10 in CXCL13-knockout EAU mice.
Conclusion
These findings underline the crucial role of CXCL13 in the pathogenesis of intraocular inflammation in VKH patients. Targeting CXCL13 may be a new therapeutic strategy for this disease.
Conflict of interest
No
1
Last name
DENG
Initials of first name(s)
Yang
Department
The First Affiliated Hospital of Chongqing Medical University
City
Chongqing
Country
China
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