{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:13:19Z","timestamp":1768518799166,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,3]]},"group-title":"Immunology","reference-count":86,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Corneal lubrication is the most common treatment for relieving the signs and symptoms of dry eye and is considered to be largely palliative with no regenerative functions. Here we challenge this notion by demonstrating that wetting the desiccated cornea of an aqueous-deficient mouse model with the simplest form of lubrication, a saline-based solution, is sufficient to rescue the severely disrupted collagen-rich architecture of the stroma, the largest corneal compartment that is essential to transparency and vision. At the single cell level we show that stromal keratocytes responsible for maintaining stromal integrity are converted from an inflammatory state into unique reparative cell states by lubrication alone, thus revealing the extensive plasticity of these cells and the regenerative function of lubricating the surface. We further show that the generation of a reparative phenotype is due, in part, to disruption of an IL1\u03b2 autocrine amplification loop promoting chronic inflammation. Thus, our study uncovers the regenerative potential of topical lubrication in dry eye and represents a paradigm shift in our understanding of its therapeutic impact.<\/jats:p>","DOI":"10.1101\/2024.11.29.626078","type":"posted-content","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T21:28:53Z","timestamp":1733261333000},"source":"Crossref","is-referenced-by-count":1,"title":["Rebuilding the autoimmune-damaged corneal stroma through topical lubrication"],"prefix":"10.64898","author":[{"given":"Yael","family":"Efraim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feeling Yu","family":"Ting Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyyed Vahid","family":"Niknezhad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ka Neng","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luye","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanan","family":"Sinada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy A.","family":"McNamara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-083X","authenticated-orcid":false,"given":"Sarah M.","family":"Knox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024120422205676000_2024.11.29.626078v1.1","doi-asserted-by":"publisher","DOI":"10.4103\/IJO.IJO_2808_22"},{"key":"2024120422205676000_2024.11.29.626078v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2022.106206"},{"key":"2024120422205676000_2024.11.29.626078v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111307"},{"key":"2024120422205676000_2024.11.29.626078v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108137"},{"key":"2024120422205676000_2024.11.29.626078v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.06.021"},{"key":"2024120422205676000_2024.11.29.626078v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-009-0011-x"},{"key":"2024120422205676000_2024.11.29.626078v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-01015-w"},{"key":"2024120422205676000_2024.11.29.626078v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.03.010"},{"key":"2024120422205676000_2024.11.29.626078v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102500"},{"key":"2024120422205676000_2024.11.29.626078v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00004-4"},{"key":"2024120422205676000_2024.11.29.626078v1.11","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030990"},{"key":"2024120422205676000_2024.11.29.626078v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.05.014"},{"key":"2024120422205676000_2024.11.29.626078v1.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184916"},{"key":"2024120422205676000_2024.11.29.626078v1.14","first-page":"192","article-title":"Dry eye syndrome","volume":"6","year":"2011","journal-title":"J. Ophthalmic Vis. Res"},{"key":"2024120422205676000_2024.11.29.626078v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2007.09.015"},{"key":"2024120422205676000_2024.11.29.626078v1.16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0117"},{"key":"2024120422205676000_2024.11.29.626078v1.17","first-page":"549","article-title":"Healing corneas express embryonic fibronectin isoforms in the epithelium, subepithelial stroma, and endothelium","volume":"149","year":"1996","journal-title":"Am. J. Pathol"},{"key":"2024120422205676000_2024.11.29.626078v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2007.04.003"},{"key":"2024120422205676000_2024.11.29.626078v1.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-016-2426-6"},{"key":"2024120422205676000_2024.11.29.626078v1.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2004281117"},{"issue":"141618","key":"2024120422205676000_2024.11.29.626078v1.21","first-page":"e141618","article-title":"Loss of Fas signaling in fibroblasts impairs homeostatic fibrosis resolution and promotes persistent pulmonary fibrosis","volume":"6","year":"2020","journal-title":"JCI Insight"},{"key":"2024120422205676000_2024.11.29.626078v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0077-z"},{"key":"2024120422205676000_2024.11.29.626078v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e13397"},{"key":"2024120422205676000_2024.11.29.626078v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.406"},{"key":"2024120422205676000_2024.11.29.626078v1.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.220046"},{"key":"2024120422205676000_2024.11.29.626078v1.26","doi-asserted-by":"publisher","DOI":"10.3390\/biology13030144"},{"key":"2024120422205676000_2024.11.29.626078v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.07.003"},{"key":"2024120422205676000_2024.11.29.626078v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.11.038"},{"key":"2024120422205676000_2024.11.29.626078v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.05.003"},{"key":"2024120422205676000_2024.11.29.626078v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2023.05.005"},{"key":"2024120422205676000_2024.11.29.626078v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2021.03.010"},{"key":"2024120422205676000_2024.11.29.626078v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03549-5"},{"key":"2024120422205676000_2024.11.29.626078v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"2024120422205676000_2024.11.29.626078v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.81"},{"key":"2024120422205676000_2024.11.29.626078v1.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209095"},{"key":"2024120422205676000_2024.11.29.626078v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.01.146"},{"key":"2024120422205676000_2024.11.29.626078v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154402"},{"key":"2024120422205676000_2024.11.29.626078v1.38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00445.2019"},{"key":"2024120422205676000_2024.11.29.626078v1.39","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-017-0299-0"},{"key":"2024120422205676000_2024.11.29.626078v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62263-8"},{"key":"2024120422205676000_2024.11.29.626078v1.41","doi-asserted-by":"publisher","DOI":"10.1111\/J.1582-4934.2010.01063.X"},{"key":"2024120422205676000_2024.11.29.626078v1.42","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0999"},{"key":"2024120422205676000_2024.11.29.626078v1.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204134120"},{"key":"2024120422205676000_2024.11.29.626078v1.44","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12010"},{"key":"2024120422205676000_2024.11.29.626078v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00782-9"},{"key":"2024120422205676000_2024.11.29.626078v1.46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00367.x"},{"key":"2024120422205676000_2024.11.29.626078v1.47","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0379TR"},{"key":"2024120422205676000_2024.11.29.626078v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.12.010"},{"key":"2024120422205676000_2024.11.29.626078v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08247-x"},{"key":"2024120422205676000_2024.11.29.626078v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0614-x"},{"key":"2024120422205676000_2024.11.29.626078v1.51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00182"},{"key":"2024120422205676000_2024.11.29.626078v1.52","doi-asserted-by":"publisher","DOI":"10.3390\/biom9020038"},{"key":"2024120422205676000_2024.11.29.626078v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.020"},{"key":"2024120422205676000_2024.11.29.626078v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"2024120422205676000_2024.11.29.626078v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16466-4"},{"key":"2024120422205676000_2024.11.29.626078v1.56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01339"},{"key":"2024120422205676000_2024.11.29.626078v1.57","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-014-0110-2"},{"key":"2024120422205676000_2024.11.29.626078v1.58","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-017-9570-7"},{"key":"2024120422205676000_2024.11.29.626078v1.59","first-page":"2745","article-title":"Physiological expression of lens \u03b1-, \u03b2-, and \u03b3- crystallins in murine and human corneas","volume":"16","year":"2010","journal-title":"Mol. Vis"},{"key":"2024120422205676000_2024.11.29.626078v1.60","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201605119"},{"key":"2024120422205676000_2024.11.29.626078v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2021.151694"},{"key":"2024120422205676000_2024.11.29.626078v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2007.09.007"},{"key":"2024120422205676000_2024.11.29.626078v1.63","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00797-1"},{"key":"2024120422205676000_2024.11.29.626078v1.64","doi-asserted-by":"crossref","unstructured":"Weber, A. , Wasiliew, P. & Kracht, M . Interleukin-1 (IL-1) Pathway. Sci. Signal. 3, (2010).","DOI":"10.1126\/scisignal.3105cm1"},{"key":"2024120422205676000_2024.11.29.626078v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.189"},{"key":"2024120422205676000_2024.11.29.626078v1.66","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.18100"},{"key":"2024120422205676000_2024.11.29.626078v1.67","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061257"},{"key":"2024120422205676000_2024.11.29.626078v1.68","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149538"},{"key":"2024120422205676000_2024.11.29.626078v1.69","first-page":"481","article-title":"Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases","volume":"3","year":"2022","journal-title":"Med N. Y. N"},{"key":"2024120422205676000_2024.11.29.626078v1.70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.15.6768"},{"key":"2024120422205676000_2024.11.29.626078v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0378-1"},{"key":"2024120422205676000_2024.11.29.626078v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.01.004"},{"key":"2024120422205676000_2024.11.29.626078v1.73","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02777-3"},{"key":"2024120422205676000_2024.11.29.626078v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.034"},{"key":"2024120422205676000_2024.11.29.626078v1.75","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-773846"},{"key":"2024120422205676000_2024.11.29.626078v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.047"},{"key":"2024120422205676000_2024.11.29.626078v1.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.02.014"},{"key":"2024120422205676000_2024.11.29.626078v1.78","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11880-9"},{"key":"2024120422205676000_2024.11.29.626078v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"2024120422205676000_2024.11.29.626078v1.80","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7113-8_28"},{"key":"2024120422205676000_2024.11.29.626078v1.81","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113628"},{"key":"2024120422205676000_2024.11.29.626078v1.82","first-page":"15","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","year":"2013","journal-title":"Bioinforma. Oxf. Engl"},{"key":"2024120422205676000_2024.11.29.626078v1.83","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2024120422205676000_2024.11.29.626078v1.84","unstructured":"Kolde, Raivo , and Maintainer Raivo Kolde . \u201cPackage \u2018pheatmap\u2019\u201d. R package 1.7 (2015): 790."},{"key":"2024120422205676000_2024.11.29.626078v1.85","unstructured":"Kevin Blighe (2019). EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling. R package version 1.2.0. https:\/\/github.com\/kevinblighe\/EnhancedVolcano"},{"key":"2024120422205676000_2024.11.29.626078v1.86","doi-asserted-by":"crossref","unstructured":"Huynh-Thu, V\u00e2n Anh , et al. \u201cInferring regulatory networks from expression data using tree-based methods.\u201d PloS one 5.9 (2010): e12776.","DOI":"10.1371\/journal.pone.0012776"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.11.29.626078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:34:19Z","timestamp":1768462459000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.11.29.626078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,3]]},"references-count":86,"URL":"https:\/\/doi.org\/10.1101\/2024.11.29.626078","relation":{},"subject":[],"published":{"date-parts":[[2024,12,3]]},"subtype":"preprint"}}