{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:03:34Z","timestamp":1791198214730,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"abstract":"<jats:p>\n                    Regulatory T (Treg) cells play a key role in immune tolerance and homeostasis. They prevent exaggerated immune responses, autoimmunity, and are crucial in graft\u2010versus\u2010host responses. On the other hand, their presence in many tumors is associated with a poor prognosis. In aged individuals, Treg populations are modified with a strong bias toward an effector phenotype and a reduced number of na\u00efve Treg cells, but little is known about the functionality of human Treg cells in old age. The low frequency of Treg cells in human peripheral blood is the main limitation to studying them. Therefore, the development of induced Treg (iTreg) cells has become a valuable tool for\n                    <jats:italic>in vitro<\/jats:italic>\n                    research on peripheral Treg cells. Following a gold\u2010standard protocol to generate iTreg\n                    <jats:italic>in vitro<\/jats:italic>\n                    , we aimed to investigate age\u2010related differences in the generation of iTreg cells. However, we detected some unexpected results regarding Foxp3 induction and iTreg functionality. We found no differences in Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    generated cells between young and older individuals. Surprisingly, the presence of the cytokine TGF\u2010\u03b2 did not play a role in either Foxp3 expression levels or in the suppressive activity of the resulting cells, regardless of the age of the donors. Therefore, we hypothesize that Foxp3 alone does not adequately define\n                    <jats:italic>bona fide<\/jats:italic>\n                    iTreg cells, and the presence of TGF\u2010\u03b2 is not essential for the\n                    <jats:italic>in vitro<\/jats:italic>\n                    differentiation of human conventional CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells into suppressive Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    cells.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70349","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:49:47Z","timestamp":1791197387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    generation of regulatory T\u00a0cells: A challenging tool for studying immune aging in humans"],"prefix":"10.1002","author":[{"given":"Lynn","family":"Muller","sequence":"first","affiliation":[{"name":"Institute for Biomedical Aging Research University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Bleher","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Aging Research University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7084-946X","authenticated-orcid":false,"given":"Birgit","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Aging Research University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4754-1202","authenticated-orcid":false,"given":"Lourdes","family":"Rocamora\u2010Reverte","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Aging Research University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.616949","article-title":"The complex role of regulatory T\u00a0cells in immunity and aging","volume":"11","author":"Rocamora\u2010Reverte L","year":"2021","journal-title":"Front Immunol"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T\u00a0cells: mechanisms of differentiation and function","volume":"30","author":"Josefowicz SZ","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.immuni.2004.07.009","article-title":"Recognition of the peripheral self by naturally arising CD25+ CD4+ T\u00a0cell receptors","volume":"21","author":"Hsieh 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