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The role of dendritic cells in non‐infectious anterior uveitis
Author(s) -
O'Rourke M.,
Canavan M.,
Sweeney C.,
Fletcher J.,
Fearon U.,
Murphy C.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0450
Subject(s) - cd80 , cd11c , cd40 , immunology , dendritic cell , cd86 , flow cytometry , antigen presenting cell , t cell , cd8 , antigen , inflammation , immune system , biology , cytotoxic t cell , medicine , phenotype , in vitro , biochemistry , gene
Purpose Noninfectious uveitis is characterised by influx of inflammatory cells into the immune‐privileged ocular microenvironment. Dendritic cells ( DC ) are powerful antigen presenting cells ( APC s) 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 CD 11c+. CD 40, CD 80 and CD 83 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 (mo DC ) model obtained from a healthy donor for 48 hours and activation and maturation markers on mo DC assessed. Results There is a decrease in circulating DC in AU patients compared to HC (p < 0.01). Circulating AU DC express higher CD 40 (p < 0.05). Inflamed AqH contains >98% CD 45+ cells. Populations of neutrophils ( CD 15+ HLA ‐ DR ‐), T cells ( CD 3+ and either CD 4+ or CD 8+) and APC s ( HLA ‐ DR + CD 11c+) were identified. HC AqH is devoid of CD 45+ cells. AU AqH induces CD 40 (p < 0.01) and CD 80 (p < 0.01) expression on mo DC 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 CD 4+ T cell cocultures. These results suggest DC may be a useful therapeutic target in AU .