{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:42:57Z","timestamp":1785530577845,"version":"3.56.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Foxp3 is regarded as the major transcription factor for T regulatory (T<jats:sub>reg<\/jats:sub>) cells and expression of Foxp3 is used to identify and quantitate Treg cells in mouse models. However, several studies have demonstrated that human CD4<jats:sup>+<\/jats:sup> T conventional (T<jats:sub>conv<\/jats:sub>) cells activated <jats:italic>in vitro<\/jats:italic> by T cell receptor (TCR) stimulation can express Foxp3. This observation has raised doubt as to the suitability of Foxp3 as a T<jats:sub>reg<\/jats:sub> marker in man. Helios, a member of the Ikaros gene family, has been shown to be expressed by 80-90% of human Foxp3<jats:sup>+<\/jats:sup> T<jats:sub>reg<\/jats:sub> cells and can potentially serve as a marker of human T<jats:sub>reg<\/jats:sub>. Here, we confirm that Foxp3 expression is readily upregulated by T<jats:sub>conv<\/jats:sub> upon TCR stimulation <jats:italic>in vitro<\/jats:italic>, while Helios expression is not altered. More importantly, we show that Foxp3 expression is not elevated by stimulation of hT<jats:sub>conv<\/jats:sub> in a humanized mouse model of graft versus host disease (GVHD) and in patients with a wide variety of acute and chronic inflammatory diseases including sickle cell disease, acute and chronic GVHD, systemic lupus erythematosus, as well as critical COVID-19. In all patients studied, an excellent correlation was observed between the percentage of CD4<jats:sup>+<\/jats:sup> T cells expressing Foxp3 and the percentage expressing Helios. Taken together, these studies demonstrate that Foxp3 is not induced upon T<jats:sub>conv<\/jats:sub> cell activation <jats:italic>in vivo<\/jats:italic> and that Foxp3 expression alone can be used to quantitate T<jats:sub>reg<\/jats:sub> cells in humans. Nevertheless, the combined use of Foxp3 and Helios expression provides a more reliable approach for the characterization of T<jats:sub>reg<\/jats:sub> in humans.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1114780","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T06:48:24Z","timestamp":1686120504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Co-expression of Foxp3 and Helios facilitates the identification of human T regulatory cells in health and disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Lyra","family":"Morina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalyn 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