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

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 anterior uveitis 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.


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In contrast, the cellular infiltrate in B27-AU and B27+AAU patients' AqH was of considerably more 178 lymphoid origin reflecting their autoimmune etiology ( Fig. 2A,B). When systematically comparing fragility of these cells during processing for scRNA-seq 31 . Overall, diverse subtypes of uveitis are 193 characterized by a unique pattern of local inflammatory cells.

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Specific transcriptional phenotype of intraocular leukocytes in subtypes of uveitis.

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Next, we sought to understand how local leukocytes differ transcriptionally in diverse uveitis entities.

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To analytically account for low total cell numbers, we merged clusters into five broad cell type 'meta-198 clusters' only for differential expression analysis (

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We also found elevated expression of prefoldin 5 (PFDN5) in myeloid, toxic and help cluster (Suppl. 220 Tab.5), which was recently described as a specific marker for B27+AAU associated with SpA 38 .

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We also attempted to understand how uveitis controlled the local inter-cellular signaling circuitry. We  Next, we tested for differences of predicted interactions between both subtypes of uveitis. Therefore, 245 we calculated the number of predicted interactions in B27+AAU minus those in B27-AU. (Fig 4A).

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Next, we sought to supplement the transcriptional data with protein information of soluble mediators.

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We therefore quantified a predefined set of cytokines in the AqH of these patient groups (Suppl. Tab.