Goblet cells contribute to ocular surface immune tolerance—implications for dry eye disease
Barbosa, Flavia L.; Xiao, Yangyan; Bian, Fang; Coursey, Terry G.; Ko, Byung Yi; Clevers, Hans; de Paiva, Cintia S.; Pflugfelder, Stephen C.
(2017) International journal of molecular sciences, volume 18, issue 5, pp. 1 - 13
(Article)
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
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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.
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Keywords: Adaptive immunity, Antigen, Dendritic cells, Goblet cell, Immune tolerance, Mucins, Catalysis, Molecular Biology, Computer Science Applications, Spectroscopy, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry, Journal Article
ISSN: 1661-6596
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: This work was supported by NIH Grant EY11915 (SCP), NIH Core Grants-EY002520 & EY020799, NIH Training Grant T32 AI053831 (FB), NIH funding to Cytometry and Cell Sorting Core at Baylor College of Medicine (NIAID P30AI036211, NCI P30CA125123, and NCRR S10RR024574), Biology of Inflammation Center Baylor College of Medicine, an unrestricted grant from Research to Prevent Blindness, New York, NY, USA (SCP), the Oshman Foundation, Houston, TX, USA (SCP), the William Stamps Farish Fund, Houston, TX, USA (SCP), the Hamill Foundation, Houston, TX, USA (SCP), and the Sid W. Richardson Foundation, Ft Worth, TX, USA (SCP). The authors thank Jeffrey Whitsett, Cincinnati Children?s Hospital, Cincinnati, OH for providing the Spdef ?/? mice, Ralph M. Nichols for assistance with transmission electron microscopy and Mahira Zaheer for her technical assistance. Publisher Copyright: © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
(Peer reviewed)