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 aging model to investigate the effects of aging on antigen presenting cells (APCs) and generation of pathogenic T helper (Th)-1 cells. 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 Th-17 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⁺ cells into young, naive immunodeficient recipients caused greater goblet cell loss than young CD4⁺CXCR3⁺ donor cells. Our results demonstrate that age-associated changes in APCs are critical for the pathogenesis of age-related dry eye.