Single-cell RNA sequencing reveals the distinctive roles of CD4+and CD8+T cells in autoimmune uveitis

Abstract

AbstractUveitis is a common cause of blindness and classified as infectious or non-infectious types. Non-infectious uveitis is often secondary to systemic autoimmune diseases, with Behçet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKHD) as the two most common causes. Uveitis in BD and VKHD often show similar clinical manifestations, but the underlying immunopathogenesis remains unclear. We collected immune cell infiltrates in aqueous humour of BD and VKHD uveitis patients and analysed them by single-cell RNA paired with T cell receptor (TCR) sequencing. T cells were found as the dominant immune cell infiltration. Intriguingly, a majority of CD4+in T cell infiltrates was only observed in VKHD but not in BD. In agreement with this discrepancy between VKHD and BD, T cell clonality analysis and Clonotype Neighbour Graph Analysis (CoNGA) also revealed a selective expansion of pro-inflammatory CD4+T cell clones in VKHD. In contrast, BD showed a selective expansion of pro-inflammatory CD8+T cell clones. Our study reveals distinct immunopathogenesis of uveitis driven by CD4+T cells in VKHD and by CD8+T cells in BD, and therefore suggests differential approaches for their diagnosis and therapy.