Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease

Flavia L Barbosa, Yangyan Xiao, Fang Bian, Terry G Coursey, Byung Yi Ko, Hans Clevers, Cintia S de Paiva, Stephen C Pflugfelder

Research output: Contribution to journal/periodicalArticleScientificpeer-review

74 Citations (Scopus)

Abstract

Conjunctival goblet cell (GC) loss in dry eye is associated with ocular surface inflammation. This study investigated if conjunctival GCs contribute to ocular surface immune tolerance. Antigens applied to the ocular surface, imaged by confocal microscopy, passed into the conjunctival stroma through goblet cell associated passages (GAPs) in wild type C57BL/6 (WT), while ovalbumin (OVA) was retained in the epithelium of SAM pointed domain containing ETS transcription factor (Spdef) knockout mice (Spdef-/-) that lack GCs and are a novel model of dry eye. Stimulated GC degranulation increased antigen binding to GC mucins. Induction of tolerance to topically applied OVA measured by cutaneous delayed type hypersensitivity (DTH) was observed in WT, but not Spdef-/-. OTII CD4⁺ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of Spdef-/- had greater IFN-γ production and lower Foxp3 positivity than those primed by WT DCs. These findings indicate that conjunctival GCs contribute to ocular surface immune tolerance by modulating antigen distribution and antigen specific immune response. GC loss may contribute to the abrogation of ocular surface immune tolerance that is observed in dry eye.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume18
Issue number5
DOIs
Publication statusPublished - 05 May 2017

Keywords

  • Journal Article

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