{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:55:03Z","timestamp":1792014903076,"version":"4.4.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005426","name":"Association for Research in Vision and Ophthalmology","doi-asserted-by":"publisher","award":["Roche Collaborative Research Fellowship 2018"],"award-info":[{"award-number":["Roche Collaborative Research Fellowship 2018"]}],"id":[{"id":"10.13039\/100005426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2013\u20101436"],"award-info":[{"award-number":["PICT 2013\u20101436"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2015\u20100971"],"award-info":[{"award-number":["PICT 2015\u20100971"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2018\u201002911"],"award-info":[{"award-number":["PICT 2018\u201002911"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Dry eye disease (DED) is a highly prevalent ocular surface disorder with neuroimmune pathophysiology. Tear hyperosmolarity (THO), a frequent finding in affected patients, is considered a key element in DED pathogenesis, yet existing animal models are based on subjecting the ocular surface to the more complex desiccating stress \u2212 decreased tear production and\/or increased evaporation \u2212 instead of strict hyperosmolar stress. Here we characterized a murine model of THO that does not involve desiccating stress, thus allowing us to dissect the contribution of THO to DED. Our results showed that THO is sufficient to disrupt neuroimmune homeostasis of the ocular surface in mice, and thus reproduce many sub\u2010clinical DED findings. THO activated nuclear factor\u2010\u03baB signalling in conjunctival epithelial cells and increased dendritic cell recruitment and maturation, leading to more activated (CD69<jats:sup>+<\/jats:sup>) and memory (CD62lo CD44hi) CD4<jats:sup>+<\/jats:sup> T\u2010cells in the eye\u2010draining lymph nodes. Ultimately, THO impaired the development of ocular mucosal tolerance to a topical surrogate antigen in a chain of events that included epithelial nuclear factor\u2010\u03baB signalling and activation of transient receptor potential vanilloid 1 as the probable hypertonicity sensor. Also, THO reduced the density of corneal intraepithelial nerves and terminals, and sensitized the ocular surface to hypertonicity. Finally, the adoptive transfer of T\u2010cells from THO mice to na\u00efve recipients under mild desiccating stress favoured DED development, showing that THO is enough to trigger an actual pathogenic T\u2010cell response. Our results altogether demonstrate that THO is a critical initiating factor in DED development.<\/jats:p>","DOI":"10.1111\/imm.13243","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T20:50:35Z","timestamp":1595537435000},"page":"148-161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Transient tear hyperosmolarity disrupts the neuroimmune homeostasis of the ocular surface and facilitates dry eye onset"],"prefix":"10.1111","volume":"161","author":[{"given":"Mauricio","family":"Guzm\u00e1n","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiliano","family":"Miglio","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Keitelman","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Maiumi","family":"Shiromizu","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Sabbione","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anal\u00eda S.","family":"Trevani","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirta N.","family":"Giordano","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5118-2540","authenticated-orcid":false,"given":"Jerem\u00edas G.","family":"Galletti","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunidad Innata Instituto de Medicina Experimental Academia Nacional de Medicina\/CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1504"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5390"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ICL.0000162759.79740.46"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0299"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e318030d259"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.08.019"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0419"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-16967"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/oem.2004.016030"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206541"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.5301\/ejo.5000525"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2013.05.040"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400016"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3838"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12716"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.9.4543"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.44"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14075"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12759"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.07.004"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.07.084"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.10.001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-1260"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0251"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0040-5"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13844"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.11.007"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2009.12.010"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1281"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.01.024"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.19-26631"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.03.006"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.11.002"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4389"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2689"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.11.001"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.4"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.61"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1905"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12491"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101442"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjophth-2017-000078"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2722"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17433"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2020.05.012"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22550"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2014.957776"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5801"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.01.028"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.3950"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.20"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14481"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00742"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36414"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-7048"},{"key":"e_1_2_10_59_1","first-page":"136929","article-title":"Allergen\u2010induced dendritic cell migration is controlled through Substance P release by sensory neurons","author":"Aderhold PA","year":"2020","journal-title":"bioRxiv"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18383"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.08.018"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-03-00951.1997"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e318181ae60"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2017.1377261"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-11322"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13243","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.13243","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T03:42:40Z","timestamp":1693885360000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,14]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/imm.13243"],"URL":"https:\/\/doi.org\/10.1111\/imm.13243","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,14]]},"assertion":[{"value":"2020-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}