Single-cell sequencing of non-infectious and viral uveitis defines distinct mechanisms in ocular inflammation

Introduction Intraocular inflammation can arise from various conditions and can lead to severe vision loss and blindness. The differences in the intraocular immune response between infectious and autoimmune etiologies have not been defined. Methods Here we use single-cell RNA sequencing to compare the innate and adaptive immune response across 73 ocular and blood samples from 35 individuals with viral uveitis, autoimmune uveitis, or non-ocular inflammatory disease. Results This atlas suggests that viral uveitis is dominated by an influx of myeloid cells that activate cytotoxic CD8 T cells via antigen presentation, while in autoimmune uveitis, dendritic cells appear to activate both type 17 and regulatory CD4 T cells. Paired VDJ sequencing revealed that, while T-cell differentiation is modulated by etiology, B cells initiate similar responses between autoimmune and viral uveitis but differ by the degree of clonal expansion and somatic hypermutation. Discussion Collectively, these data identify the differences in innate and adaptive immune responses based on the intraocular stimulus.