The Role of Antigen Presenting Cells in the Pathophysiology of Dry Eye

Abstract

PurposeDry eye (DE) disease is perpetuated by self‐antigen driven autoimmune‐based inflammation. During the initiation of desiccating stress (DS)‐induced DE acute cytokine production and dendritic cell activation precedes autoreactive CD4 + T cell activation, and CD4 + T cells isolated from these DE mice are sufficient to mediate disease following adoptive transfer to T cell‐deficient nude recipient mice.MethodsFlow cytometry, IHC, ELISA and ocular surface antigen presenting cell (APC)‐depletion were used to phenotype expression and function of dendritic cells and cytokines during DS‐DE (induced in C57BL/6 female mice exposed to sc scopolamine (0.5 mg/0.2 ml) TID, humidity <40%, and sustained airflow).ResultsIn response to DS‐induced DE there is a significant increase (p ≤ 0.05) in the expression of CD11cloPDCA+ plasmacytoid dendritic cells (pDCs) and secretion of type I interferons (IFNa/b) in draining cervical lymph nodes (CLN) and ocular surface tissues compared to naïve controls. The higher frequency of pDCs within the CLN correlated with enhanced IFNa levels in both CLN and ocular surface tears (p ≤ 0.05). Furthermore, CD4 + T cells isolated from APC‐depleted mice exposed to DS are not pathogenic; CD4 + T cell infiltration was markedly (p < 0.05) reduced relative to controls, which was associated with an attenuated proinflammatory cytokine/chemokine response.ConclusionsCollectively, these data further support the concept that DE is a localized self‐antigen‐driven autoimmune disease.