Intra-ocular dendritic cells are increased in HLA-B27 associated acute anterior uveitis

Abstract

Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. HLA-B27-associated Uveitis is a common subtype of uveitis and a prototypical ocular autoimmune 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 and negative AU and an infectious endophthalmitis control by combining single cell RNA sequencing (scRNA-seq) with flow cytometry and low-input proteomics. Ocular cell infiltrates consisted primarily of lymphocytes in uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured an plasmacytoid and classical dendritic cells (cDC) infiltrate, and of plasma cells. Moreover, cDCs were central in predicted local cell-cell communication. The data suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of particular dendritic cells.

Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

“…Indeed, emerging single cell analysis of ocular fluids of patients support the infiltration of CD1c+ DC subsets in the eye during autoimmune uveitis (42), and we show that these cells express CD36 and CX3CR1 (Fig. 4G).…”

“…We speculated that the decrease in blood CD36+CX3CR1+ CD1c+ DCs was a result from migration of these cells to the eye during autoimmune uveitis. Recent single-cell RNA sequencing data by Kasper and co-workers in eye biopsies of autoimmune uveitis patients show infiltration in the eye by conventional dendritic cells, which are transcriptionally similar to CD1c+ DCs (42). Reanalysis of this data using CLEC10A as a specific marker for CD1c+ DCs in tissues (43) showed that eye-infiltrating CD1c+ DC cells express CD36 and CX3CR1 (Fig.…”