{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:28Z","timestamp":1785413668158,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,20]]},"group-title":"Immunology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Eye Institute (NEI), National Institutes of Health","award":["R01EY011386"],"award-info":[{"award-number":["R01EY011386"]}]},{"name":"National Eye Institute (NEI), National Institutes of Health","award":["R01EY026635"],"award-info":[{"award-number":["R01EY026635"]}]},{"name":"National Eye Institute (NEI), National Institutes of Health","award":["P30EY029220"],"award-info":[{"award-number":["P30EY029220"]}]},{"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health","award":["F31DK138790-01"],"award-info":[{"award-number":["F31DK138790-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>To characterize tear proteome changes in male non-obese diabetic (NOD) mice with Sj\u00f6gren\u2019s disease (SjD)-like autoimmune dacryoadenitis and determine whether identified tear proteins are associated with lacrimal gland (LG) pathogenesis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Tears were collected from 14-week-old male NOD mice and age-matched male BALB\/c controls and analyzed by tandem mass tag (TMT)-based liquid chromatography tandem mass spectrometry (LC-MS\/MS). Differentially expressed proteins (DEPs) were defined using adjusted\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05 and absolute fold change &gt; 1.5. Functional enrichment analysis was performed using Enrichr. Selected upregulated DEPs were further examined in tear and LG samples from independent mouse cohorts using Western blotting, immunofluorescence, and RT-qPCR.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    A total of 142 proteins were quantified across all tear samples. Hierarchical clustering and principal component analysis (PCA) separated NOD from BALB\/c tear proteomes. A total of 41 proteins were differentially expressed in NOD mouse tears (33 increased, 8 decreased). Increased tear proteins were enriched in immune and inflammatory responses, secretory compartments, RAGE receptor binding, glutathione metabolism, oxidative stress, and redox regulation. S100A8\/A9, GSTO1-1, Gal-3, and pIgR\/secretory component (SC) were increased in both NOD mouse tears and LG. In NOD LG, increased S100A8\/A9 was accompanied by elevated RAGE, whereas increased GSTO1-1 was associated with increased NLRP3, cleaved caspase-1, cleaved gasdermin, cleaved IL-1\u03b2, and increased\n                    <jats:italic>Il1b<\/jats:italic>\n                    ,\n                    <jats:italic>Il18<\/jats:italic>\n                    , and\n                    <jats:italic>Il18r<\/jats:italic>\n                    gene expression.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Male NOD mouse tears contain disease-related proteins reflecting pathological inflammatory and epithelial changes in the LG including increased RAGE signaling, NLRP3 inflammasome activation, and altered epithelial transcytosis.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.15.738677","type":"posted-content","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:25:16Z","timestamp":1784611516000},"source":"Crossref","is-referenced-by-count":0,"title":["Tear Proteomics Reveals RAGE and NLRP3 Inflammasome Pathway Activation in Lacrimal Glands of a Sj\u00f6gren\u2019s Disease Mouse Model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8829-057X","authenticated-orcid":false,"given":"Xiaoyang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, United States"},{"name":"Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy, University of Southern California, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Alba","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy, University of Southern California, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison V.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Abdelhamid","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, United States"},{"name":"Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy, University of Southern California, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Pasarow Mass Spectrometry Laboratory and Neuropsychiatric Institute-Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Edman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Whitelegge","sequence":"additional","affiliation":[{"name":"Pasarow Mass Spectrometry Laboratory and Neuropsychiatric Institute-Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F.","family":"Hamm-Alvarez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, United States"},{"name":"Department of Pharmacology and Pharmaceutical Sciences, Alfred E. 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