Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27 positive (n=3) and negative (n=2) anterior uveitis and an infectious endophthalmitis control (n=1) by combining single cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured a plasmacytoid and classical dendritic cells (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of dendritic cells. Overall design: Single-cell RNA profiling of intraokular leukocytes from HLA-B27 positive (n=3) compared with HLA-B27 negative (n = 2) anterior uveitis and an infectious endophthalmitis (n=1)