{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:32:16Z","timestamp":1791261136780,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T00:00:00Z","timestamp":1493942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY11915"],"award-info":[{"award-number":["EY11915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY002520"],"award-info":[{"award-number":["EY002520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY020799"],"award-info":[{"award-number":["EY020799"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212\/\u2212) 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\u2212\/\u2212. OTII CD4+ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of Spdef\u2212\/\u2212 had greater IFN-\u03b3 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.<\/jats:p>","DOI":"10.3390\/ijms18050978","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T10:31:08Z","timestamp":1493980268000},"page":"978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Goblet Cells Contribute to Ocular Surface Immune Tolerance\u2014Implications for Dry Eye Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Flavia","family":"Barbosa","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Coursey","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Ophthalmology, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 302-718, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Clevers","sequence":"additional","affiliation":[{"name":"Hubrecht Institute, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-5494","authenticated-orcid":false,"given":"Cintia","family":"De Paiva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Pflugfelder","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,5]]},"reference":[{"key":"ref_1","first-page":"40","article-title":"Mucous glycoproteins: A gel of a problem","volume":"20","author":"Carlstedt","year":"1985","journal-title":"Essays Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1097\/OPX.0000000000000664","article-title":"Altered Mucin and Glycoprotein Expression in Dry Eye Disease","volume":"92","author":"Stephens","year":"2015","journal-title":"Optom. 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