{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:02:15Z","timestamp":1784772135470,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T00:00:00Z","timestamp":1539993600000},"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":["EY027731"],"award-info":[{"award-number":["EY027731"]}],"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":["EY05612"],"award-info":[{"award-number":["EY05612"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1037321"],"award-info":[{"award-number":["1037321"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1042735"],"award-info":[{"award-number":["1042735"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sj\u00f6gren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (Cxcl9, Ccl19) and other potentially disease-relevant genes (Epsti1, Ubd) were upregulated in male lacrimal glands. Expression of Cxcl9 and Ccl19, in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, Ifnar1-deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.<\/jats:p>","DOI":"10.3390\/ijms19103259","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T08:43:36Z","timestamp":1540284216000},"page":"3259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sj\u00f6gren Syndrome"],"prefix":"10.3390","volume":"19","author":[{"given":"Yury","family":"Chaly","sequence":"first","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1688-730X","authenticated-orcid":false,"given":"Jennifer Y.","family":"Barr","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-3778","authenticated-orcid":false,"given":"David A.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen E.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Medicine, St. Vincent\u2019s Hospital, St. Vincent\u2019s Institute, The University of Melbourne, Fitzroy, Victoria 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-315X","authenticated-orcid":false,"given":"Thomas C.","family":"Brodnicki","sequence":"additional","affiliation":[{"name":"Department of Medicine, St. Vincent\u2019s Hospital, St. Vincent\u2019s Institute, The University of Melbourne, Fitzroy, Victoria 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-7582","authenticated-orcid":false,"given":"Scott M.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1001\/jama.2013.278448","article-title":"Autoantibodies present before symptom onset in primary Sjogren syndrome","volume":"310","author":"Jonsson","year":"2013","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/art.39214","article-title":"Prediction of Sjogren\u2019s Syndrome Years Before Diagnosis and Identification of Patients with Early Onset and Severe Disease Course by Autoantibody Profiling","volume":"67","author":"Theander","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s13075-015-0678-2","article-title":"The clinical relevance of animal models in Sjogren\u2019s syndrome: The interferon signature from mouse to man","volume":"17","author":"Maria","year":"2015","journal-title":"Arthritis Res. 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