{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:59:59Z","timestamp":1791928799017,"version":"4.3.4"},"reference-count":49,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2022,6,10]]},"DOI":"10.1167\/iovs.63.6.12","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T11:33:37Z","timestamp":1654860817000},"page":"12","source":"Crossref","is-referenced-by-count":42,"title":["PPAR-\u03b1 Agonist Fenofibrate Ameliorates Sj\u00f6gren Syndrome\u2013Like Dacryoadenitis by Modulating Th1\/Th17 and Treg Cell Responses in NOD Mice"],"prefix":"10.1167","volume":"63","author":[{"given":"Xingyi","family":"Guo","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Dang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deming","family":"Sun","sequence":"additional","affiliation":[{"name":"Doheny Eye Institute, And Department of Ophthalmology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Nian","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Wei","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jtos.2014.12.001","article-title":"Clinical guidelines for management of dry eye associated with Sjogren disease","volume":"13","author":"Foulks","year":"2015","journal-title":"Ocul Surf"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.rdc.2018.03.002","article-title":"Update on Sjogren syndrome and other causes of sicca in older adults","volume":"44","author":"Baer","year":"2018","journal-title":"Rheum Dis Clin North Am"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jaut.2009.09.009","article-title":"Sjogren syndrome: advances in the pathogenesis from animal models","volume":"33","author":"Chiorini","year":"2009","journal-title":"J Autoimmun"},{"issue":"7","key":"bib5","doi-asserted-by":"publisher","first-page":"3088","DOI":"10.1093\/rheumatology\/kez004","article-title":"T cells in primary Sjogren's syndrome: targets for early intervention","volume":"60","author":"Verstappen","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaut.2017.11.003","article-title":"Th17 cells in primary Sjogren's syndrome: pathogenicity and plasticity","volume":"87","author":"Verstappen","year":"2018","journal-title":"J Autoimmun"},{"key":"bib7","first-page":"263","article-title":"Activity of T-helper cells in patients with primary Sjogren's syndrome","volume":"27","author":"Sudzius","year":"2013","journal-title":"In Vivo"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1136\/annrheumdis-2018-213036","article-title":"Short-term and low-dose IL-2 therapy restores the Th17\/Treg balance in the peripheral blood of patients with primary Sjogren's syndrome","volume":"77","author":"Miao","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1111\/imm.2015.145.issue-2","article-title":"Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjogren syndrome","volume":"145","author":"Lieberman","year":"2015","journal-title":"Immunology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.jconrel.2017.05.007","article-title":"Treg-recruiting microspheres prevent inflammation in a murine model of dry eye disease","volume":"258","author":"Ratay","year":"2017","journal-title":"J Control Release"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/jim.2007.262.issue-2","article-title":"PPARs and their metabolic modulation: new mechanisms for transcriptional regulation?","volume":"262","author":"Ahmed","year":"2007","journal-title":"J Intern Med"},{"key":"bib12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.5114\/ceji.2016.58817","article-title":"Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg\/Th17 disorder","volume":"41","author":"Cheng","year":"2016","journal-title":"Cent Eur J Immunol"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1053\/j.gastro.2007.03.113","article-title":"Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice","volume":"133","author":"Lee","year":"2007","journal-title":"Gastroenterology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"e0208399","DOI":"10.1371\/journal.pone.0208399","article-title":"Neuroprotective effects of PPARalpha in retinopathy of type 1 diabetes","volume":"14","author":"Pearsall","year":"2019","journal-title":"PLoS One"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.exer.2013.06.005","article-title":"Amniotic membrane extract ameliorates benzalkonium chloride-induced dry eye in a murine model","volume":"115","author":"Xiao","year":"2013","journal-title":"Exp Eye Res"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.jconrel.2013.07.016","article-title":"A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjogren's syndrome","volume":"171","author":"Shah","year":"2013","journal-title":"J Control Release"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1172\/JCI1230","article-title":"Male gonadal environment paradoxically promotes dacryoadenitis in nonobese diabetic mice","volume":"101","author":"Hunger","year":"1998","journal-title":"J Clin Invest"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"154338","DOI":"10.1016\/j.metabol.2020.154338","article-title":"The role of peroxisome proliferator-activated receptors (PPAR) in immune responses","volume":"114","author":"Christofides","year":"2021","journal-title":"Metabolism"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.atherosclerosis.2009.01.008","article-title":"On the mechanism for PPAR agonists to enhance ABCA1 gene expression","volume":"205","author":"Ogata","year":"2009","journal-title":"Atherosclerosis"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41385-020-0323-5","article-title":"Liver X receptor regulates Th17 and RORgammat(+) Treg cells by distinct mechanisms","volume":"14","author":"Parigi","year":"2021","journal-title":"Mucosal Immunol"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1172\/JCI35288","article-title":"Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice","volume":"119","author":"Korf","year":"2009","journal-title":"J Clin Invest"},{"issue":"14","key":"bib22","doi-asserted-by":"publisher","first-page":"5093","DOI":"10.3390\/ijms21145093","article-title":"Combination of peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonists prevents corneal inflammation and neovascularization in a rat alkali burn model","volume":"21","author":"Nakano","year":"2020","journal-title":"Int J Mol Sci"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/aos.v98.4","article-title":"Evidence and indications for systemic treatment in diabetic retinopathy: a systematic review","volume":"98","author":"Elkjaer","year":"2020","journal-title":"Acta Ophthalmol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1016\/S0140-6736(07)61607-9","article-title":"Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial","volume":"370","author":"Keech","year":"2007","journal-title":"Lancet"},{"key":"bib25","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1056\/NEJMoa1001288","article-title":"Effects of medical therapies on retinopathy progression in type 2 diabetes","volume":"363","author":"Group","year":"2010","journal-title":"N Engl J Med"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1167\/iovs.61.3.54","article-title":"PPAR-alpha agonist fenofibrate suppressed the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride","volume":"61","author":"He","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1016\/j.ajpath.2020.09.002","article-title":"High-fat diet-induced functional and pathologic changes in lacrimal gland","volume":"190","author":"He","year":"2020","journal-title":"Am J Pathol"},{"issue":"17","key":"bib28","doi-asserted-by":"publisher","first-page":"9584","DOI":"10.3390\/ijms22179584","article-title":"CD4(+) T-cell plasticity in non-infectious retinal inflammatory disease","volume":"22","author":"Chen","year":"2021","journal-title":"Int J Mol Sci"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"102933","DOI":"10.1016\/j.autrev.2021.102933","article-title":"Autoimmunity in dry eye disease\u2014an updated review of evidence on effector and memory Th17 cells in disease pathogenicity","volume":"20","author":"Chen","year":"2021","journal-title":"Autoimmun Rev"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1002\/art.40165","article-title":"Attenuation of follicular helper T cell-dependent B cell hyperactivity by abatacept treatment in primary Sjogren's syndrome","volume":"69","author":"Verstappen","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1080\/03009740801910361","article-title":"Immunological alterations in newly diagnosed primary Sjogren's syndrome characterized by skewed peripheral T-cell subsets and inflammatory cytokines","volume":"37","author":"Szodoray","year":"2008","journal-title":"Scand J Rheumatol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"7319","DOI":"10.1038\/s41598-019-43714-5","article-title":"Elevated cytokine levels in tears and saliva of patients with primary Sjogren's syndrome correlate with clinical ocular and oral manifestations","volume":"9","author":"Chen","year":"2019","journal-title":"Sci Rep"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.yexcr.2018.12.005","article-title":"PPARalpha suppresses Th17 cell differentiation through IL-6\/STAT3\/RORgammat pathway in experimental autoimmune myocarditis","volume":"375","author":"Chang","year":"2019","journal-title":"Exp Cell Res"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"5189","DOI":"10.4049\/jimmunol.1500449","article-title":"Antagonizing peroxisome proliferator-activated receptor alpha activity selectively enhances Th1 immunity in male mice","volume":"195","author":"Zhang","year":"2015","journal-title":"J Immunol"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.coi.2009.03.001","article-title":"Transcriptional regulatory networks in Th17 cell differentiation","volume":"21","author":"Zhou","year":"2009","journal-title":"Curr Opin Immunol"},{"issue":"19","key":"bib36","doi-asserted-by":"publisher","first-page":"7015","DOI":"10.3390\/ijms21197015","article-title":"Treg enhancing therapies to treat autoimmune diseases","volume":"21","author":"Eggenhuizen","year":"2020","journal-title":"Int J Mol Sci"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/j.1365-2249.2009.03966.x","article-title":"Cells with regulatory function of the innate and adaptive immune system in primary Sjogren's syndrome","volume":"157","author":"Szodoray","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"bib38","first-page":"529035","article-title":"Fenofibrate enhances the in vitro differentiation of foxp3(+) regulatory T cells in mice","volume":"2012","author":"Zhou","year":"2012","journal-title":"PPAR Res"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.molmed.2007.08.005","article-title":"TGFbeta1 and Treg cells: alliance for tolerance","volume":"13","author":"Bommireddy","year":"2007","journal-title":"Trends Mol Med"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1084\/jem.20030152","article-title":"Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3","volume":"198","author":"Chen","year":"2003","journal-title":"J Exp Med"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nrrheum.2014.105","article-title":"TREG-cell therapies for autoimmune rheumatic diseases","volume":"10","author":"Miyara","year":"2014","journal-title":"Nat Rev Rheumatol"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"5494","DOI":"10.1167\/iovs.18-24504","article-title":"Sleep deprivation induces dry eye through inhibition of PPARalpha expression in corneal epithelium","volume":"59","author":"Tang","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.ijpddr.2017.10.003","article-title":"Treatment with fenofibrate plus a low dose of benznidazole attenuates cardiac dysfunction in experimental Chagas disease","volume":"7","author":"Cevey","year":"2017","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"e46615","DOI":"10.1371\/journal.pone.0046615","article-title":"LXR-mediated inhibition of CD4+ T helper cells","volume":"7","author":"Solt","year":"2012","journal-title":"PLoS One"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"e0184985","DOI":"10.1371\/journal.pone.0184985","article-title":"Liver X receptor activation promotes differentiation of regulatory T cells","volume":"12","author":"Herold","year":"2017","journal-title":"PLoS One"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1172\/JCI42974","article-title":"Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation","volume":"121","author":"Cui","year":"2011","journal-title":"J Clin Invest"},{"issue":"4","key":"bib47","doi-asserted-by":"publisher","first-page":"e20201311","DOI":"10.1084\/jem.20201311","article-title":"Nuclear receptor LXRbeta controls fitness and functionality of activated T cells","volume":"218","author":"Michaels","year":"2021","journal-title":"J Exp Med"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1161\/01.ATV.0000210278.67076.8f","article-title":"LXR activation reduces proinflammatory cytokine expression in human CD4-positive lymphocytes","volume":"26","author":"Walcher","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S1097-2765(01)00164-2","article-title":"A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis","volume":"7","author":"Chawla","year":"2001","journal-title":"Mol Cell"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2778897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:31Z","timestamp":1791927091000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2778897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.63.6.12","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}