{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:02:28Z","timestamp":1775840548631,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Natural Science Research Project of Anhui Educational Committee"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myasthenia gravis (MG) is an autoimmune disease commonly associated with immune disorders in thymoma. The role of thymus myoid cells (TMCs) in the pathogenesis of autoimmune diseases has attracted much attention. Therefore, the present study was designed to reveal the impact of TMCs on the pathophysiology of tumor-associated MG (TAMG). This study included clinical patients and healthy volunteers and validated the potential role of TMCs in TAMG progression using a TMCs-deficient mouse model. Correlative findings showed that TMCs deletion affected thymic architecture in MG patients, as evidenced by the expression of key myogenic factors as well as AChR and RyRs receptors in the thymus. Further experimental validation showed that TMCs deletion increased the levels of Th1 and Th17 cells, decreased the levels of Th2 and Treg cells, and altered the secretion of corresponding cytokines, including IL-2, IL-4, IL-17, IL-22, and TGF-\u03b2 concentrations. Co-culture of CD4+ T cells with Thy0517 cells or CD4+ T cells with a myoblastoid cell line using the Transwell system demonstrated that deletion of TMC inhibited the differentiation of CD4+ T cells to Treg cells. In this study, we hypothesized that TMCs are involved in TAMG progression by regulating CD4+ T cell differentiation.<\/jats:p>","DOI":"10.1093\/cei\/uxaf043","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T14:35:04Z","timestamp":1750775704000},"source":"Crossref","is-referenced-by-count":1,"title":["Deletion of thymic myoid cells regulates the thymic microenvironment involved in the progression of tumor-associated myasthenia gravis"],"prefix":"10.1093","volume":"219","author":[{"given":"Bo","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyu","family":"Ding","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Anhui Medical University , Hefei, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8506-3194","authenticated-orcid":false,"given":"Li","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"2025072106112090500_CIT0001","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.expneurol.2018.11.006","article-title":"Tacrolimus inhibits Th1 and Th17 responses in MuSK-antibody positive myasthenia gravis patients","volume":"312","author":"Li","year":"2019","journal-title":"Exp Neurol"},{"key":"2025072106112090500_CIT0002","doi-asserted-by":"publisher","first-page":"828970","DOI":"10.3389\/fneur.2022.828970","article-title":"The LINC00452\/miR-204\/CHST4 axis regulating thymic Tregs might be involved in the progression of thymoma-associated myasthenia gravis","volume":"13","author":"Wang","year":"2022","journal-title":"Front Neurol"},{"key":"2025072106112090500_CIT0003","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/S1474-4422(15)00145-3","article-title":"Myasthenia gravis: subgroup classification and therapeutic strategies","volume":"14","author":"Gilhus","year":"2015","journal-title":"Lancet Neurol"},{"key":"2025072106112090500_CIT0004","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.autrev.2013.03.007","article-title":"The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes","volume":"12","author":"Marx","year":"2013","journal-title":"Autoimmun Rev"},{"key":"2025072106112090500_CIT0005","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s00281-021-00842-3","article-title":"Thymus and autoimmunity","volume":"43","author":"Marx","year":"2021","journal-title":"Semin Immunopathol"},{"key":"2025072106112090500_CIT0006","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/S0002-9440(10)65225-X","article-title":"Establishment of a human thymic myoid cell line. Phenotypic and functional characteristics","volume":"155","author":"Wakkach","year":"1999","journal-title":"Am J Pathol"},{"key":"2025072106112090500_CIT0007","first-page":"167","article-title":"Phenotypic and functional characterization of human thymic stromal cell lines","volume":"47","author":"Wakkach","year":"2001","journal-title":"Cell Mol Biol (Noisy-le-grand)"},{"key":"2025072106112090500_CIT0008","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.jneuroim.2003.11.013","article-title":"Thymic myoid cells express high levels of muscle genes","volume":"148","author":"Mesnard-Rouiller","year":"2004","journal-title":"J Neuroimmunol"},{"key":"2025072106112090500_CIT0009","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3109\/08916930903555935","article-title":"Thymoma and paraneoplastic myasthenia gravis","volume":"43","author":"Marx","year":"2010","journal-title":"Autoimmunity"},{"key":"2025072106112090500_CIT0010","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1172\/JCI29894","article-title":"Myasthenia gravis: past, present, and future","volume":"116","author":"Conti-Fine","year":"2006","journal-title":"J Clin Invest"},{"key":"2025072106112090500_CIT0011","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41572-019-0079-y","article-title":"Myasthenia gravis","volume":"5","author":"Gilhus","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2025072106112090500_CIT0012","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12974-024-03194-5","article-title":"FOSL1-mediated LINC01566 negatively regulates CD4(+) T-cell activation in myasthenia gravis","volume":"21","author":"Li","year":"2024","journal-title":"J Neuroinflammation"},{"key":"2025072106112090500_CIT0013","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1182\/blood.V96.12.3872","article-title":"Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease","volume":"96","author":"Hoffacker","year":"2000","journal-title":"Blood"},{"key":"2025072106112090500_CIT0014","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/ana.1017","article-title":"Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis","volume":"50","author":"Buckley","year":"2001","journal-title":"Ann Neurol"},{"key":"2025072106112090500_CIT0015","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1212\/wnl.44.4.728","article-title":"Organ-specific autoantigens induce interferon-gamma and interleukin-4 mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis","volume":"44","author":"Link","year":"1994","journal-title":"Neurology"},{"key":"2025072106112090500_CIT0016","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/j.1365-3083.2012.02703.x","article-title":"T helper type 17 cells expand in patients with myasthenia-associated thymoma","volume":"76","author":"Wang","year":"2012","journal-title":"Scand J Immunol"},{"key":"2025072106112090500_CIT0017","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1007\/s10875-012-9685-0","article-title":"Changes of Treg-associated molecules on CD4+CD25 +Treg cells in myasthenia gravis and effects of immunosuppressants","volume":"32","author":"Xu","year":"2012","journal-title":"J Clin Immunol"},{"key":"2025072106112090500_CIT0018","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.expneurol.2015.12.010","article-title":"Myf5 and Myogenin in the development of thymic myoid cells\u2014implications for a murine in vivo model of myasthenia gravis","volume":"277","author":"Hu","year":"2016","journal-title":"Exp Neurol"},{"key":"2025072106112090500_CIT0019","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/1759-7714.12163","article-title":"Establishment and characterization of a novel cell line derived from thymoma with myasthenia gravis patients","volume":"6","author":"Wang","year":"2015","journal-title":"Thorac Cancer"},{"key":"2025072106112090500_CIT0020","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.3390\/jcm10112235","article-title":"Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations","volume":"10","author":"Dresser","year":"2021","journal-title":"J Clin Med"},{"key":"2025072106112090500_CIT0021","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jaut.2013.12.015","article-title":"Both Treg cells and Tconv cells are defective in the myasthenia gravis thymus: roles of IL-17 and TNF-alpha","volume":"52","author":"Gradolatto","year":"2014","journal-title":"J Autoimmun"},{"key":"2025072106112090500_CIT0022","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/nyas.13591","article-title":"An imbalance between regulatory T cells and T helper 17 cells in acetylcholine receptor-positive myasthenia gravis patients","volume":"1413","author":"Villegas","year":"2018","journal-title":"Ann N Y Acad Sci"},{"key":"2025072106112090500_CIT0023","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1111\/ene.14820","article-title":"Clinical characteristics and outcomes of thymoma-associated myasthenia gravis","volume":"28","author":"Alvarez-Velasco","year":"2021","journal-title":"Eur J Neurol"},{"key":"2025072106112090500_CIT0024","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/nyas.13519","article-title":"Thymus involvement in early-onset myasthenia gravis","volume":"1412","author":"Cron","year":"2018","journal-title":"Ann N Y Acad Sci"},{"key":"2025072106112090500_CIT0025","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jneuroim.2004.01.022","article-title":"Thymic myoid cells as a myasthenogenic antigen and antigen-presenting cells","volume":"150","author":"Matsumoto","year":"2004","journal-title":"J Neuroimmunol"},{"key":"2025072106112090500_CIT0026","doi-asserted-by":"publisher","first-page":"893","DOI":"10.2353\/ajpath.2007.070240","article-title":"Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status","volume":"171","author":"Leite","year":"2007","journal-title":"Am J Pathol"},{"key":"2025072106112090500_CIT0027","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1001\/jamaneurol.2016.0603","article-title":"Frequency of synaptic autoantibody accompaniments and neurological manifestations of thymoma","volume":"73","author":"Zekeridou","year":"2016","journal-title":"JAMA Neurol"},{"key":"2025072106112090500_CIT0028","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.clim.2015.12.009","article-title":"MiR-15a contributes abnormal immune response in myasthenia gravis by targeting CXCL10","volume":"164","author":"Liu","year":"2016","journal-title":"Clin Immunol"},{"key":"2025072106112090500_CIT0029","doi-asserted-by":"publisher","first-page":"6893","DOI":"10.4049\/jimmunol.166.11.6893","article-title":"Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4","volume":"166","author":"Im","year":"2001","journal-title":"J Immunol"},{"key":"2025072106112090500_CIT0030","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.4049\/jimmunol.0903111","article-title":"Activation of tolerogenic dendritic cells in the tumor draining lymph nodes by CD8+ T cells engineered to express CD40 ligand","volume":"184","author":"Higham","year":"2010","journal-title":"J Immunol"},{"key":"2025072106112090500_CIT0031","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.clim.2019.05.006","article-title":"Inhibition of ROCK activity regulates the balance of Th1, Th17 and Treg cells in myasthenia gravis","volume":"203","author":"Song","year":"2019","journal-title":"Clin Immunol"},{"key":"2025072106112090500_CIT0032","doi-asserted-by":"publisher","first-page":"113146","DOI":"10.1016\/j.expneurol.2019.113146","article-title":"Inhibition of the transcription factor ROR-gamma reduces pathogenic Th17 cells in acetylcholine receptor antibody positive myasthenia gravis","volume":"325","author":"Yi","year":"2020","journal-title":"Exp Neurol"},{"key":"2025072106112090500_CIT0033","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1007\/s10072-017-3009-3","article-title":"High frequencies of circulating Tfh-Th17 cells in myasthenia gravis patients","volume":"38","author":"Yang","year":"2017","journal-title":"Neurol Sci"},{"key":"2025072106112090500_CIT0034","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jneuroim.2010.03.016","article-title":"Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients","volume":"225","author":"Masuda","year":"2010","journal-title":"J Neuroimmunol"},{"key":"2025072106112090500_CIT0035","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1002\/eji.201445064","article-title":"IL-17-producing CD4(+) T cells contribute to the loss of B-cell tolerance in experimental autoimmune myasthenia gravis","volume":"45","author":"Schaffert","year":"2015","journal-title":"Eur J Immunol"},{"key":"2025072106112090500_CIT0036","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1002\/ana.20340","article-title":"Selective loss of regulatory T cells in thymomas","volume":"56","author":"Strobel","year":"2004","journal-title":"Ann Neurol"},{"key":"2025072106112090500_CIT0037","first-page":"103","article-title":"Characterization of a macrophage lineage cell colony-stimulating factor produced by thymic myoid cells","volume":"79","author":"Kamo","year":"1993","journal-title":"Immunology"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cei\/advance-article-pdf\/doi\/10.1093\/cei\/uxaf043\/63571256\/uxaf043.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/219\/1\/uxaf043\/63571256\/uxaf043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/219\/1\/uxaf043\/63571256\/uxaf043.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:11:28Z","timestamp":1753092688000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/doi\/10.1093\/cei\/uxaf043\/8173035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,21]]}},"URL":"https:\/\/doi.org\/10.1093\/cei\/uxaf043","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"uxaf043"}}