The role of dendritic cells in non-infectious anterior uveitis
Abstract
Purpose
Noninfectious uveitis is characterised by influx of inflammatory cells into the immune-privileged ocular microenvironment. Dendritic cells (DC) are powerful antigen presenting cells (APCs) and thereby initiate and perpetuate inflammation. Animal models of uveitis have suggested alterations in DC contribute to pathogenesis. Firstly, we examine the phenotype of circulating DC in anterior uveitis (AU). Secondly, we characterise the influxing inflammatory cells in the local micro-environment of inflamed aqueous humor (AqH). Finally, the effect of this inflamed microenvironment on a DC model is examined.
Methods
Circulating DC were defined as HLA-DR+, Lineage- and CD11c+. CD40, CD80 and CD83 cell surface expression was used to assess activation and maturation of circulating DC. Cells isolated from AqH obtained from AU patients (n = 5) and HC were assessed by flow cytometry based on cell size, granularity and cell surface expression. 1:2 dilution of AqH supernatant was cultured with monocyte derived DC (moDC) model obtained from a healthy donor for 48 hours and activation and maturation markers on moDC assessed.
Results
There is a decrease in circulating DC in AU patients compared to HC (p < 0.01). Circulating AU DC express higher CD40 (p < 0.05). Inflamed AqH contains >98% CD45+ cells. Populations of neutrophils (CD15+ HLA-DR-), T cells (CD3+ and either CD4+ or CD8+) and APCs (HLA-DR+ CD11c+) were identified. HC AqH is devoid of CD45+ cells. AU AqH induces CD40 (p < 0.01) and CD80 (p < 0.01) expression on moDC compared to HC.
Conclusions
These results suggest that DC are recruited from the circulation to the eye during AU. AqH from AU patients can activate DC which will lead to initiation and propagation of inflammation. Current work examines functional effects on allogenic CD4+ T cell cocultures. These results suggest DC may be a useful therapeutic target in AU.
