{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:52:07Z","timestamp":1788209527573,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondi di Ateneo per la Ricerca","award":["FAR2021"],"award-info":[{"award-number":["FAR2021"]}]},{"name":"Fondi di Ateneo per la Ricerca","award":["FAR2022"],"award-info":[{"award-number":["FAR2022"]}]},{"name":"University of Insubria","award":["FAR2021"],"award-info":[{"award-number":["FAR2021"]}]},{"name":"University of Insubria","award":["FAR2022"],"award-info":[{"award-number":["FAR2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves\u2019 disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs\u2019 functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD.<\/jats:p>","DOI":"10.3390\/ijms242216432","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:49:47Z","timestamp":1700182187000},"page":"16432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Regulatory T Cells in the Pathogenesis of Graves\u2019 Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-5238","authenticated-orcid":false,"given":"Natasa","family":"Kustrimovic","sequence":"first","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Disease\u2014CAAD, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1873-3048","authenticated-orcid":false,"given":"Daniela","family":"Gallo","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Piantanida","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Bartalena","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Lai","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Zerbinati","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7551-1751","authenticated-orcid":false,"given":"Maria Laura","family":"Tanda","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-7101","authenticated-orcid":false,"given":"Lorenzo","family":"Mortara","sequence":"additional","affiliation":[{"name":"Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.4049\/jimmunol.163.10.5211","article-title":"Induction of tumor immunity by removing CD25+CD4+ T cells: A common basis between tumor immunity and autoimmunity","volume":"163","author":"Shimizu","year":"1999","journal-title":"J. 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