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Int. J. Mol. Sci. 2017, 18(5), 978; doi:10.3390/ijms18050978

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

1
Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA
2
Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, China
3
Department of Ophthalmology, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 302-718, Korea
4
Hubrecht Institute, 3584 CT Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Igor A. Butovich
Received: 8 April 2017 / Revised: 27 April 2017 / Accepted: 2 May 2017 / Published: 5 May 2017
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders)
View Full-Text   |   Download PDF [4292 KB, uploaded 5 May 2017]   |  

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. View Full-Text
Keywords: mucins; antigen; goblet cell; dendritic cells; adaptive immunity; immune tolerance mucins; antigen; goblet cell; dendritic cells; adaptive immunity; immune tolerance
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Barbosa, F.L.; Xiao, Y.; Bian, F.; Coursey, T.G.; Ko, B.Y.; Clevers, H.; de Paiva, C.S.; Pflugfelder, S.C. Goblet Cells Contribute to Ocular Surface Immune Tolerance—Implications for Dry Eye Disease. Int. J. Mol. Sci. 2017, 18, 978.

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