Age-associated antigen-presenting cell alterations promote dry-eye inducing Th1 cells

• Published in: Mucosal immunology Vol. 12; no. 4; pp. 897 - 908
• Main Authors: Bian, Fang, Xiao, Yangyan, Barbosa, Flavia L., de Souza, Rodrigo G., Hernandez, Humberto, Yu, Zhiyuan, Pflugfelder, Stephen C., de Paiva, Cintia S.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2019; Elsevier Limited
• Subjects: Adoptive Transfer; Age; Aging; Aging - genetics; Aging - immunology; Aging - metabolism; Aldehyde dehydrogenase; Allergology; Animals; Antibodies; Antigen presentation; Antigen-presenting cells; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens; Biomarkers; Biomedical and Life Sciences; Biomedicine; CCR6 protein; CD4 antigen; CD86 antigen; Cellular Senescence - genetics; Cellular Senescence - immunology; Conjunctiva; CXCR3 protein; Cytokines - metabolism; Disease Models, Animal; Dry Eye Syndromes - etiology; Dry Eye Syndromes - metabolism; Dry Eye Syndromes - physiopathology; Dry Eye Syndromes - therapy; Female; Gastroenterology; Immunodeficiency; Immunology; Lacrimal gland and Nasolacrimal duct; Lymph nodes; Lymphatic system; Lymphocyte Activation; Lymphocytes T; Mice; Mice, Knockout; Ovalbumin; Risk factors; Th1 Cells - immunology; Th1 Cells - metabolism; γ-Interferon
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-018-0127-z

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.