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A. R. Hajrasouliha, Z. Sadrai, D. R. Saban, S. K. Chauhan, R. Dana; The Role of Chemokine Decoy Receptor D6 on Leukocytes in Regulating Corneal Inflammation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6142.
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D6 is a decoy receptor which functions to regulate immunity by scavenging numerous inflammatory chemokines (i.e. CCL2, CLL3, CCL4, and CCCL5). While D6 expression was first shown on lymphatic endothelial cells, it has also been shown on a variety of leukocytes as well. We therefore hypothesized that D6 expression plays a role in controlling inflammation in the cornea and dendritic cells (DCs) are important in mediating this response.
Corneal inflammation was induced using the suture-model, whereby 3 intra-stromal sutures are placed in the paracentral cornea. Expression of D6 in normal and inflamed corneas as well as their draining lymph nodes was analyzed by RT-PCR out to10 days post-surgery. Additionally, the phenotype of D6-expressing cells was identified by flow cytometry via double-staining with various relevant cell-surface markers (i.e. CD45, CD3, CD11c and CD11b).
Infiltration of leukocytes (CD45+) into the cornea was detected 24 hours post-surgery and this was associated with a two-fold increase in D6 expression (p<0.05, as measured by RT-PCR). Moreover, these mice also exhibited on day 7 post-surgery, increased D6 expression on MHC II+ cells of the draining lymph node. Interestingly, D6 expression proved to be strongly enhanced in lymph node DCs (CD11c+) draining from inflamed corneas, as compared to the naïve controls (mean fluorescence = 139.5 vs. 97, respectively).
Our data points to the possibility that D6 plays a role in controlling corneal inflammation, as it is strongly up-regulated during an inflammatory insult. Moreover, it appears that this level of regulation may be offered particularly by DCs, which appear to express the highest levels of this scavenger receptor. Future work is now aimed at testing this hypothesis in a D6 knock-out model, which we have recently acquired.
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