Age-associated Antigen-presenting Cell Alterations Promote Dry-eye Inducing Th1 Cells

Overview

Journal Mucosal Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2019 Jan 31

PMID 30696983

Citations 29

Authors

Fang Bian

Yangyan Xiao

Flavia L Barbosa

Rodrigo G de Souza

Humberto Hernandez

Zhiyuan Yu

Stephen C Pflugfelder

Cintia S de Paiva

Affiliations

Soon will be listed here.

Abstract

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 CD4T cells, while Th-17 cells were present only in aged draining nodes. There was also an age-related increase in CD4CXCR3IFN-γ cells in the conjunctiva, nodes, and lacrimal glands while CD4CCR6IL-17A cells increased in the draining nodes of aged mice. Adoptive transfer of aged CD4CXCR3 cells into young, naive immunodeficient recipients caused greater goblet cell loss than young CD4CXCR3 donor cells. Our results demonstrate that age-associated changes in APCs are critical for the pathogenesis of age-related dry eye.

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