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Canonical regulatory T cells express CD4, FOXP3, and CD25, which are considered definitive markers of their regulatory T-cell status when expressed together. However, a subset of noncanonical regulatory T cells expressing only CD4 and FOXP3 have recently been described in some infection contexts.<\/jats:p>\n                  <jats:p>Using a unique mouse model for the first time demonstrated that the TCF-1 regulation of regulatory T-cell suppressive function is not limited to the thymus during development. Our data showed that TCF-1 also regulated regulatory T cells\u2019 suppressive ability in secondary organs and graft-vs-host disease target organs as well as upregulating noncanonical regulatory T cells. Our data demonstrated that TCF-1 regulates the suppressive function of regulatory T cells through critical molecules like GITR and PD-1, specifically by means of noncanonical regulatory T cells. Our in vitro approaches show that TCF-1 regulates the regulatory T-cell effector-phenotype and the molecules critical for regulatory T-cell migration to the site of inflammation.<\/jats:p>\n                  <jats:p>Using in vivo models, we show that both canonical and noncanonical regulatory T cells from TCF-1 cKO mice have a superior suppressive function, as shown by their ability to control conventional T-cell proliferation, avert acute graft-vs-host disease, and limit tissue damage. Thus, for the first time, we provide evidence that TCF-1 negatively regulates the suppressive ability of canonical and noncanonical regulatory T cells. These findings provide evidence that TCF-1 is a novel target for developing strategies to treat alloimmune disorders.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad019","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T11:19:28Z","timestamp":1676459968000},"page":"489-503","source":"Crossref","is-referenced-by-count":15,"title":["TCF-1 negatively regulates the suppressive ability of canonical and noncanonical Tregs"],"prefix":"10.1093","volume":"113","author":[{"given":"Mahinbanu","family":"Mammadli","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University , 766 Irving Ave, Weiskotten Hall Suite 2281, Syracuse, NY 13210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liye","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of Pathology, SUNY Upstate Medical University , 766 Irving Ave, Weiskotten Hall Suite 2141, Syracuse, NY 13210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti Misra","family":"Sen","sequence":"additional","affiliation":[{"name":"National Institute on Aging-National Institutes of Health , BRC Building, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224 , USA"},{"name":"Center of Aging and Immune Remodeling and Immunology Program, Department of Medicine, Johns Hopkins School of Medicine , 2024 E, Monument Street Suite 2-700, Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-4814","authenticated-orcid":false,"given":"Mobin","family":"Karimi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, SUNY Upstate Medical University , 766 Irving Ave, Weiskotten Hall Suite 2281, Syracuse, NY 13210 , 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