Age-associated Antigen-Presenting Cell Alterations Promote Dry-Eye Inducing Th1 cells

Aging is a significant risk factor for dry eye. Here we used a murine aged mode to investigate the effects of aging on antigen presenting cells (APCs) and generation of pathogenic T helper (Th)1. Our results showed that APCs from aged mice accumulate at the conjunctiva, have higher levels of co-activation marker CD86 and lower aldehyde dehydrogenase activity. Using topical ovalbumin peptide as a surrogate antigen, we observed an increased number of antigen-loaded APCs in the draining cervical lymph nodes in the aged group and loss of tight junction protein occludin in the conjunctiva. Aged cervical lymph nodes APCs showed a greater generation of Th1 cells than young APCs in antigen-presentation assays in vitro. Aged lacrimal glands and draining nodes showed an accumulation of IFN-γ producing CD4(+)T cells, while Th17 cells were present only in aged draining nodes. There was also an age-related increase in CD4(+)CXCR3(+)IFN-γ(+) cells in the conjunctiva, nodes and lacrimal glands while CD4(+)CCR6(+)IL-17A(+) cells increased in the draining nodes of aged mice. Adoptive transfer of aged CD4(+)CXCR3(+) donor cells into young, naive immunodeficient recipients caused greater goblet cell loss than young CD4(+)CXCR3(+) cells. Our results demonstrate that age-associated changes in APCs are critical for the pathogenesis of age-related dry eye.