Immune Responses at the Ocular Surface

Immune-mediated diseases of the ocular surface are relatively broad in their respective etiologies, which can involve infection, autoimmunity, or allergy. Despite this range, immune responses often converge upstream at the level of the dendritic cell (DC)—a highly specialized group of antigen presenting cells required in the activation of naïve T cells. Our lab has established a novel mouse model of allergic eye disease (AED), which leads to severe clinical manifestations, sustained ocular inflammation, and eosinophilic infiltration at levels seen in patients with atopic keratoconjunctivitis. Use of the AED model has led to identification of classical CD11b+ DCs as the key subset responsible for activating allergen reactive T cells. In addition, the AED model has uncovered the importance of CCR7 as the master chemokine receptor in homing of ocular surface DCs to the regional lymph nodes. Additionally, CCR7 has recently been shown to contribute to activation of Th17 cells in the mouse model of dry eye disease. Likewise, similar to the dry eye disease model, AED involves corneal lymphangiogenesis—potentially suggesting a role for corneal DCs in allergic immune responses. Thus, efforts to progress the current understanding of DC biology holds tremendous promise for advancement of novel and effective medicines in immune mediated diseases of the ocular surface.