Genetic landscape and autoimmunity of monocytes in developing Vogt–Koyanagi–Harada disease

Significance Vogt–Koyanagi–Harada (VKH) disease is one of the most common and severe vision-threatening autoimmune uveitis in Asians. However, the functional heterogeneity among subsets in human blood monocytes and the VKH disease-relevant populations remains elusive. This study encoded the landscape of human monocytes, clustered six subsets with distinct functions, and revealed two populations, using single-cell RNA sequencing. Surprisingly, we discovered a disease-specific subset, proinflammatory monocytes, implicating immune activation in VKH disease. We also identified a cell type-specific transcriptional signature in subset ISG15, which might be corresponded with treatment response. These data highlight advanced understanding of pathogenesis, mapping an atlas of autoimmune monocytes and potential therapeutic targets in autoimmune uveitis.