Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease
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...
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| Veröffentlicht in: | International journal of molecular sciences 2017-05, Vol.18 (5), p.978 |
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| creator | Barbosa, Flavia L Xiao, Yangyan Bian, Fang Coursey, Terry G Ko, Byung Yi Clevers, Hans de Paiva, Cintia S Pflugfelder, Stephen C |
| description | 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 (
) knockout mice (
/
) 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
/
. OTII CD4⁺ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of
/
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. |
| doi_str_mv | 10.3390/ijms18050978 |
| format | Article |
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) knockout mice (
/
) 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
/
. OTII CD4⁺ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of
/
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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms18050978</identifier><identifier>PMID: 28475124</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antibodies - metabolism ; Antigens ; Binding ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; Confocal microscopy ; Conjunctiva - cytology ; Conjunctiva - immunology ; Degranulation ; Dendritic cells ; Dendritic Cells - immunology ; Dry Eye Syndromes - genetics ; Dry Eye Syndromes - immunology ; Drying ; Epithelium ; ETS protein ; Eye ; Eye diseases ; Female ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Foxp3 protein ; Goblet cells ; Goblet Cells - immunology ; Hypersensitivity (delayed) ; Immune system ; Immune Tolerance ; Immunity (Disease) ; Immunological tolerance ; Interferon ; Interferon-gamma - genetics ; Interferon-gamma - metabolism ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Mice ; Mice, Inbred C57BL ; Microscopy ; Mucin ; Mucins - metabolism ; Ovalbumin ; Ovalbumin - metabolism ; Proto-Oncogene Proteins c-ets - genetics ; Rodents ; Stroma</subject><ispartof>International journal of molecular sciences, 2017-05, Vol.18 (5), p.978</ispartof><rights>Copyright MDPI AG 2017</rights><rights>2017 by the authors. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-7218216bee5cf026b9496ab1ac2da2657ca1cb20889f8cf5ad6daf510b61c0573</citedby><cites>FETCH-LOGICAL-c478t-7218216bee5cf026b9496ab1ac2da2657ca1cb20889f8cf5ad6daf510b61c0573</cites><orcidid>0000-0002-9057-5494</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454891/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454891/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28475124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barbosa, Flavia L</creatorcontrib><creatorcontrib>Xiao, Yangyan</creatorcontrib><creatorcontrib>Bian, Fang</creatorcontrib><creatorcontrib>Coursey, Terry G</creatorcontrib><creatorcontrib>Ko, Byung Yi</creatorcontrib><creatorcontrib>Clevers, Hans</creatorcontrib><creatorcontrib>de Paiva, Cintia S</creatorcontrib><creatorcontrib>Pflugfelder, Stephen C</creatorcontrib><title>Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>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 (
) knockout mice (
/
) 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
/
. OTII CD4⁺ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of
/
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.</description><subject>Animals</subject><subject>Antibodies - metabolism</subject><subject>Antigens</subject><subject>Binding</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Confocal microscopy</subject><subject>Conjunctiva - cytology</subject><subject>Conjunctiva - immunology</subject><subject>Degranulation</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dry Eye Syndromes - genetics</subject><subject>Dry Eye Syndromes - immunology</subject><subject>Drying</subject><subject>Epithelium</subject><subject>ETS protein</subject><subject>Eye</subject><subject>Eye diseases</subject><subject>Female</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Foxp3 protein</subject><subject>Goblet cells</subject><subject>Goblet Cells - immunology</subject><subject>Hypersensitivity (delayed)</subject><subject>Immune system</subject><subject>Immune Tolerance</subject><subject>Immunity (Disease)</subject><subject>Immunological tolerance</subject><subject>Interferon</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - metabolism</subject><subject>Lymph nodes</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy</subject><subject>Mucin</subject><subject>Mucins - metabolism</subject><subject>Ovalbumin</subject><subject>Ovalbumin - metabolism</subject><subject>Proto-Oncogene Proteins c-ets - genetics</subject><subject>Rodents</subject><subject>Stroma</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1LxDAQxYMoft88S8CLB6uTtEmTiyDr14LgQT15CGl2qlnaZk1aYf97K36wepqB-fGY9x4hBwxO81zDmZ-3iSkQoEu1RrZZwXkGIMv1lX2L7KQ0B-A5F3qTbHFVlILxYps834SqwZ5OsGkSnYSuj74aeqR9oPduaGykD0OsrUM6bduhQ_oYGoy2c5hN20Xjne196BKtQ6SXcUmvlkgvfUKbcI9s1LZJuP89d8nT9dXj5Da7u7-ZTi7uMleUqs9KzhRnskIUrgYuK11oaStmHZ9ZLkXpLHMVB6V0rVwt7EzObC0YVJI5EGW-S86_dBdD1eLM4WjCNmYRfWvj0gTrzd9L51_NS3g3ohCF0mwUOP4WiOFtwNSb1ic3JmI7DEMyTGkJudRCjejRP3QehtiN9gzTDCRAnsuROvmiXAwpRax_n2FgPlszq62N-OGqgV_4p6b8Ax69k9g</recordid><startdate>20170505</startdate><enddate>20170505</enddate><creator>Barbosa, Flavia L</creator><creator>Xiao, Yangyan</creator><creator>Bian, Fang</creator><creator>Coursey, Terry G</creator><creator>Ko, Byung Yi</creator><creator>Clevers, Hans</creator><creator>de Paiva, Cintia S</creator><creator>Pflugfelder, Stephen C</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9057-5494</orcidid></search><sort><creationdate>20170505</creationdate><title>Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease</title><author>Barbosa, Flavia L ; Xiao, Yangyan ; Bian, Fang ; Coursey, Terry G ; Ko, Byung Yi ; Clevers, Hans ; de Paiva, Cintia S ; Pflugfelder, Stephen C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-7218216bee5cf026b9496ab1ac2da2657ca1cb20889f8cf5ad6daf510b61c0573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antibodies - metabolism</topic><topic>Antigens</topic><topic>Binding</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Confocal microscopy</topic><topic>Conjunctiva - cytology</topic><topic>Conjunctiva - immunology</topic><topic>Degranulation</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dry Eye Syndromes - genetics</topic><topic>Dry Eye Syndromes - immunology</topic><topic>Drying</topic><topic>Epithelium</topic><topic>ETS protein</topic><topic>Eye</topic><topic>Eye diseases</topic><topic>Female</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Foxp3 protein</topic><topic>Goblet cells</topic><topic>Goblet Cells - immunology</topic><topic>Hypersensitivity (delayed)</topic><topic>Immune system</topic><topic>Immune Tolerance</topic><topic>Immunity (Disease)</topic><topic>Immunological tolerance</topic><topic>Interferon</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - metabolism</topic><topic>Lymph nodes</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy</topic><topic>Mucin</topic><topic>Mucins - metabolism</topic><topic>Ovalbumin</topic><topic>Ovalbumin - metabolism</topic><topic>Proto-Oncogene Proteins c-ets - genetics</topic><topic>Rodents</topic><topic>Stroma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barbosa, Flavia L</creatorcontrib><creatorcontrib>Xiao, Yangyan</creatorcontrib><creatorcontrib>Bian, Fang</creatorcontrib><creatorcontrib>Coursey, Terry G</creatorcontrib><creatorcontrib>Ko, Byung Yi</creatorcontrib><creatorcontrib>Clevers, Hans</creatorcontrib><creatorcontrib>de Paiva, Cintia S</creatorcontrib><creatorcontrib>Pflugfelder, Stephen C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barbosa, Flavia L</au><au>Xiao, Yangyan</au><au>Bian, Fang</au><au>Coursey, Terry G</au><au>Ko, Byung Yi</au><au>Clevers, Hans</au><au>de Paiva, Cintia S</au><au>Pflugfelder, Stephen C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2017-05-05</date><risdate>2017</risdate><volume>18</volume><issue>5</issue><spage>978</spage><pages>978-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><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 (
) knockout mice (
/
) 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
/
. OTII CD4⁺ T cells primed by dendritic cells (DCs) from the conjunctival draining lymph nodes of
/
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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>28475124</pmid><doi>10.3390/ijms18050978</doi><orcidid>https://orcid.org/0000-0002-9057-5494</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2017-05, Vol.18 (5), p.978 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Antibodies - metabolism Antigens Binding CD4 antigen CD4-Positive T-Lymphocytes - immunology Confocal microscopy Conjunctiva - cytology Conjunctiva - immunology Degranulation Dendritic cells Dendritic Cells - immunology Dry Eye Syndromes - genetics Dry Eye Syndromes - immunology Drying Epithelium ETS protein Eye Eye diseases Female Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Foxp3 protein Goblet cells Goblet Cells - immunology Hypersensitivity (delayed) Immune system Immune Tolerance Immunity (Disease) Immunological tolerance Interferon Interferon-gamma - genetics Interferon-gamma - metabolism Lymph nodes Lymphocytes Lymphocytes T Mice Mice, Inbred C57BL Microscopy Mucin Mucins - metabolism Ovalbumin Ovalbumin - metabolism Proto-Oncogene Proteins c-ets - genetics Rodents Stroma |
| title | Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease |
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