Abstract
Purpose:
This study purposed to depict the transcriptional changes associated with autoimmune uveitis (AU) pathogenesis and identify potential therapeutic targets of this disease.
Methods:
An experimental AU (EAU) model was established with retina antigen and adjuvants. An EAU control group was established with adjuvant only to eliminate nonspecific effects. We conducted single-cell RNA sequencing (scRNA-seq) on cervical draining lymph node cells of EAU, EAU control, and normal mice to identify the EAU-associated transcriptional changes and the potential pathogenic molecules. Subsequent flow cytometry, adoptive transfer experiment, scRNA-seq analysis of human uveitis, and proliferation assessment were conducted to verify the function of the interested molecule in uveitis.
Results:
The scRNA-seq data suggested that hypoxia-inducible factor 1 alpha (Hif1α) may participate in EAU pathogenesis via regulating T helper (Th)-17, Th1, and regulatory T cells. Hif1α inhibition alleviated EAU symptoms and regulated Th17, Th1, and regulatory T cell proportions. CD4+ T cells with repressed Hif1α expression failed to transfer EAU to naïve mice. In Vogt-Koyanagi-Harada disease, which is a human uveitis, Hif1α was also increased in CD4+ T cells and regulated their proliferation.
Conclusions:
The results indicate that Hif1α may participate in AU pathogenesis and are, thus, a potential therapeutic target.