Premium
The Role of Antigen Presenting Cells in the Pathophysiology of Dry Eye
Author(s) -
Stern M.E.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0251
Subject(s) - proinflammatory cytokine , immunology , adoptive cell transfer , antigen presenting cell , t cell , cytokine , antigen , chemokine , dendritic cell , flow cytometry , autoimmunity , inflammation , biology , medicine , immune system
Purpose Dry 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 CD 4 + T cell activation, and CD 4 + T cells isolated from these DE mice are sufficient to mediate disease following adoptive transfer to T cell‐deficient nude recipient mice. Methods Flow 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 C57 BL /6 female mice exposed to sc scopolamine (0.5 mg/0.2 ml) TID , humidity <40%, and sustained airflow). Results In response to DS ‐induced DE there is a significant increase ( p ≤ 0.05) in the expression of CD 11clo PDCA + plasmacytoid dendritic cells ( pDC s) and secretion of type I interferons ( IFN a/b) in draining cervical lymph nodes ( CLN ) and ocular surface tissues compared to naïve controls. The higher frequency of pDC s within the CLN correlated with enhanced IFN a levels in both CLN and ocular surface tears ( p ≤ 0.05). Furthermore, CD 4 + T cells isolated from APC ‐depleted mice exposed to DS are not pathogenic; CD 4 + T cell infiltration was markedly (p < 0.05 ) reduced relative to controls, which was associated with an attenuated proinflammatory cytokine/chemokine response. Conclusions Collectively, these data further support the concept that DE is a localized self‐antigen‐driven autoimmune disease.