{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:01:32Z","timestamp":1773262892937,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and lung tissues. Currently available drugs delay SSc progression but do not reverse the sclerotic lesions or cure the disease. Studies of its pathogenesis have been hindered by the lack of an appropriate animal model, as the widely used mouse model of bleomycin (BLM)-induced scleroderma does not reproduce the immune cell activation seen in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we describe an improved mouse model of SSc, achieved by combining BLM administration with immunization against the structural protein vimentin, injected in homogenized form with complete Freund\u2019s adjuvant (CFA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>An examination of the immune cell modifications and pathological changes in skin and lung showed both more severe fibrosis and an increase in systemic Th2 and Th17 cells and autoantibodies compared to mice treated with BLM alone. The levels of pro-inflammatory cytokines in the lesions of vimentin-immunized mice were also significantly increased.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This improved model system offers dual advantages for advancing SSc research: it enables deeper mechanistic investigation of the interconnected pathways driving both fibrosis and autoimmune activation, while simultaneously providing a more relevant preclinical platform for evaluating novel therapeutic strategies targeting multiple disease components.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1639601","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:22:20Z","timestamp":1762496540000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Vimentin immunization induces TH2\/TH17 cell activation and autoantibody production in a novel mouse model of bleomycin induced systemic sclerosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Chae Rim","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon-Yeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeonghyeon","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Deog","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Been","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Won","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Uk","family":"Seo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-La","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.974078","article-title":"Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis","volume":"13","author":"Giannini","year":"2022","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01692-0","article-title":"Systemic sclerosis","volume":"401","author":"Volkmann","year":"2023","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/s13075-021-02672-y","article-title":"Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality","volume":"23","author":"De Almeida Chaves","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"rky041","DOI":"10.1093\/rap\/rky041","article-title":"Risk factors for the development of systemic sclerosis: a systematic review of the literature","volume":"2","author":"Abbot","year":"2018","journal-title":"Rheumatol Adv Pract"},{"key":"B5","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41467-023-44645-6","article-title":"Systems-based identification of the Hippo pathway for promoting fibrotic mesenchymal differentiation in systemic sclerosis","volume":"15","author":"Ma","year":"2024","journal-title":"Nat Commun"},{"key":"B6","doi-asserted-by":"publisher","first-page":"102211","DOI":"10.1016\/j.coph.2022.102211","article-title":"Current advances in the treatment of systemic sclerosis","volume":"64","author":"Bukiri","year":"2022","journal-title":"Curr Opin Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13238","article-title":"The immunopathogenesis of fibrosis in systemic sclerosis","volume":"195","author":"Brown","year":"2019","journal-title":"Clin Exp Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00272","article-title":"Pathogenesis of systemic sclerosis","volume":"6","author":"Pattanaik","year":"2015","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663381","article-title":"Editorial: etiopathogenesis of systemic sclerosis: an update","volume":"12","author":"Stifano","year":"2021","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0346","article-title":"Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis","volume":"2","author":"Sakkas","year":"2006","journal-title":"Nat Clin Pract Rheumatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.900638","article-title":"The pathophysiological roles of regulatory T cells in the early phase of systemic sclerosis","volume":"13","author":"Kobayashi","year":"2022","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.999008","article-title":"Dysregulated B cell function and disease pathogenesis in systemic sclerosis","volume":"13","author":"Beesley","year":"2022","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-021-05665-z","article-title":"B cells in systemic sclerosis: from pathophysiology to treatment","volume":"40","author":"Melissaropoulos","year":"2021","journal-title":"Clin Rheumatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"17721","DOI":"10.1038\/s41598-019-54132-y","article-title":"TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis","volume":"9","author":"Gabsi","year":"2019","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0005903","article-title":"The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes","volume":"4","author":"Radstake","year":"2009","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213031","article-title":"Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis","volume":"77","author":"Denton","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01865","article-title":"Interleukin-6 and type-I collagen production by systemic sclerosis fibroblasts are differentially regulated by interleukin-17A in the presence of transforming growth factor-beta 1","volume":"9","author":"Dufour","year":"2018","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/j.1346-8138.2009.00764.x","article-title":"Animal model of systemic sclerosis","volume":"37","author":"Yamamoto","year":"2010","journal-title":"J Dermatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000967","article-title":"Animal models in systemic sclerosis: an update","volume":"35","author":"Bi","year":"2023","journal-title":"Curr Opin Rheumatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.145","article-title":"A modified murine model of systemic sclerosis: bleomycin given by pump infusion induced skin and pulmonary inflammation and fibrosis","volume":"95","author":"Liang","year":"2015","journal-title":"Lab Invest"},{"key":"B21","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2147\/OARRR.S50009","article-title":"Animal models of systemic sclerosis: their utility and limitations","volume":"6","author":"Artlett","year":"2014","journal-title":"Open Access Rheumatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.04.004","article-title":"Vimentin as antigenic target in autoimmunity: A comprehensive review","volume":"17","author":"Musaelyan","year":"2018","journal-title":"Autoimmun Rev"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.1988.tb03664.x","article-title":"Autoantibodies to vimentin-type intermediate filament in patients with progressive systemic sclerosis","volume":"15","author":"Tsuneda","year":"1988","journal-title":"J Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2018.1548032","article-title":"Citrullinated vimentin and biglycan protein fingerprints as candidate serological biomarkers for disease activity in systemic sclerosis: a pilot study","volume":"24","author":"Siebuhr","year":"2019","journal-title":"Biomarkers"},{"key":"B25","article-title":"Microvascular changes in progressive systemic sclerosis: immunohistochemical and ultrastructural study","volume":"2","author":"Trotta","year":"1984","journal-title":"Clin Exp Rheumatol"},{"key":"B26","first-page":"48","article-title":"Acetaminophen self-administered in the drinking water increases the pain threshold of rats (Rattus norvegicus)","volume":"45","author":"Mickley","year":"2006","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.30802\/AALAS-JAALAS-17-000118","article-title":"Analgesic efficacy of subcutaneous-oral dosage of tramadol after surgery in C57BL\/6J mice","volume":"57","author":"Evangelista-Vaz","year":"2018","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12967-021-02860-z","article-title":"Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts","volume":"19","author":"Moon","year":"2021","journal-title":"J Transl Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s12967-024-05056-3","article-title":"MicroRNA-21a-5p inhibition alleviates systemic sclerosis by targeting STAT3 signaling","volume":"22","author":"Park","year":"2024","journal-title":"J Transl Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"507","DOI":"10.2144\/000112729","article-title":"Standardized quantification of pulmonary fibrosis in histological samples","volume":"44","author":"Hubner","year":"2008","journal-title":"Biotechniques"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.14153","article-title":"Systemic sclerosis","volume":"45","author":"Asano","year":"2018","journal-title":"J Dermatol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"102526","DOI":"10.1016\/j.jaut.2020.102526","article-title":"Bi-directional communication: Conversations between fibroblasts and immune cells in systemic sclerosis","volume":"113","author":"Worrell","year":"2020","journal-title":"J Autoimmun"},{"key":"B33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s12890-023-02349-z","article-title":"Pulmonary fibrosis model of mice induced by different administration methods of bleomycin","volume":"23","author":"Gul","year":"2023","journal-title":"BMC Pulm Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701586200","article-title":"Vimentin is the specific target in skin glycation. Structural prerequisites, functional consequences, and role in skin aging","volume":"282","author":"Kueper","year":"2007","journal-title":"J Biol Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.13.2455","article-title":"Impaired wound healing in embryonic and adult mice lacking vimentin","volume":"113","author":"Eckes","year":"2000","journal-title":"J Cell Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.111.13.1897","article-title":"Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts","volume":"111","author":"Eckes","year":"1998","journal-title":"J Cell Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02095","article-title":"Formyl peptide receptor 2 activation ameliorates dermal fibrosis and inflammation in bleomycin-induced scleroderma","volume":"10","author":"Park","year":"2019","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1639601\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:22:21Z","timestamp":1762496541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1639601\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2025.1639601"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1639601","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]},"article-number":"1639601"}}