Ocular surface CD207+ cells prevent inflammatory cell infiltration and cytokine induction in dry eye mouse

Abstract

Purpose : Langerhans cells (LCs) located within the epithelial layer of normal cornea are suspected to function as one of major antigen-presenting cells (APCs) in pathologic status of ocular surface. In previous study we reported that increased infiltration and morphologic changes of epithelial DCs in dry eye (DE) were visualized by confocal microscope. It was noticeable that in DE patients with less severe symptoms, the average length of LC processes and LC areas were observed to be increased when compared to symptomatically severe DE. We performed experimental study using in vivo CD207-depleted murine DE model to investigate the functional role of LCs during ocular surface inflammation in DE disease.

Methods : C57BL/6 wild-type (WT) and CD207-depleted Langerin-diphtheria toxin receptor (CD207-DTR) mice were used in the study. To keep the depleting status of CD207+ cells in ocular surface, DT (0.1 microgram/ml) was injected every other days to the CD207-DTR mice. Before and during DE induction in mice, corneal erosion was scored with fluorescent staining. After seven days of DE induction in mice, corneas with adjacent conjunctival tissues were acquired. Inflammatory cytokines and CD4+, CD11b+, and Gr1+ cell numbers were analyzed with fluorescence activated cell sorting (FACS) and compared between WT and CD207-deleted mice after DE induction.

Results : Corneal erosion score was significantly elevated from the immediate after the DE induction in CD207+ cell depleted mice. Ocular surface IL-6 and IL-17 levels in CD207+ deleted DE-induced mice were 3.9-fold and 5.2-fold higher, respectively, than the WT DE model. TNF-a, and IL-1b levels were showed no differences. In addition, inflammatory cell (e.g., CD4+, CD11b+, and Gr1+ cells) numbers were significantly higher in langerin knockout than WT mice after DE induction.

Conclusions : We demonstrated that LCs have a role of negatively regulating ocular surface inflammation during DE disease and might be important to maintaining disease tolerability. Considering with the findings of previous clinical study, the activation parameters, rather than the cell density of corneal LCs, are important for reducing DE ocular pathology and are more valuable for measuring DE severity and predicting DE-induced immunopathologic change.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.