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Micheal O'Rourke, Mary Canavan, Ursula Fearon, Conor C Murphy; Dendritic cells in non-infectious anterior uveitis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5782.
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© ARVO (1962-2015); The Authors (2016-present)
Innate immunity is triggered when toll-like receptors (TLRs) on antigen presenting cells become activated leading to subsequent activation of inflammatory cascades. Dendritic cells (DC) are professional antigen presenting cells (APCs), which can be divided into 2 major subsets - myeloid (mDC) and plasmacytoid (pDC). TLRs promote maturation of APCs by the production of pro-inflammatory cytokines and up-regulation of co-stimulatory molecules. This study compared APC percentage, activation status and intracellular cytokine production of mDC and pDC in the circulation of AU patients to healthy controls (HCs). The inflammatory cell profile in inflamed aqueous humor (AqH) of AU patients was also carried investigated.
Circulating DC were defined as HLADR+, Lineage- and further subdivided as myeloid (CD11c+) or plasmacytoid DC (CD123+). CD40, CD80 and CD83 cell surface expression was used to assess activation and maturation status of each subtype. After cell permeabilisation, intracellular cytokine staining was carried out for IL-10 and TNFa under basal, TLR4 (LPS), TLR7/8 (Resiquimod) and TLR9 (CpG) stimulated conditions. To examine the local inflammatory response, approximately 250uL of inflamed AqH from active AU patients was centrifuged to obtain a cell pellet and stained for CD45, HLA DR and CD11c.
AU patients (n=5) had a decrease in circulating mDC and pDC compared to healthy controls (HC) (p<0.05). CD40 expression on mDC in AU patients was increased (p<0.05) with no differences in CD80 and CD83. There was no difference in IL10 or TNFa production under basal conditions. However, pDC showed hypo-responsiveness to TLR4 stimulation with lower IL10 and TNFa production in AU compared to controls (p<0.05). Inflamed AqH cells were CD45+ with approximately 1% being HLA DR+ CD11c+.
These results provide evidence that DCs are recruited to the eye from the circulation during AU with decreased numbers in circulation and a population of DC present in the inflamed AqH. Circulating DC may be tolerised to TLR4 stimulation with decreased cytokine production on stimulation. Current work is profiling cytokine concentration in AqH and the functional effect of inflamed AqH on HC monocyte derived DC model co-cultured with T cells.
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