{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:44:28Z","timestamp":1790621068121,"version":"4.1.0"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"13","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,3,29]]},"abstract":"<jats:p>\n            The maintenance of regulatory T (T\n            <jats:sub>reg<\/jats:sub>\n            ) cells critically prevents autoimmunity. Pre\u2013B cell leukemia transcription factor 1 (\n            <jats:italic>Pbx1<\/jats:italic>\n            ) variants are associated with lupus susceptibility, particularly through the expression of a dominant negative isoform\n            <jats:italic>Pbx1-d<\/jats:italic>\n            in CD4\n            <jats:sup>+<\/jats:sup>\n            T cells.\n            <jats:italic>Pbx1-d<\/jats:italic>\n            overexpression impaired T\n            <jats:sub>reg<\/jats:sub>\n            cell homeostasis and promoted inflammatory CD4\n            <jats:sup>+<\/jats:sup>\n            T cells. Here, we showed a high expression of\n            <jats:italic>Pbx1<\/jats:italic>\n            in human and murine T\n            <jats:sub>reg<\/jats:sub>\n            cells, which is decreased in lupus patients and mice.\n            <jats:italic>Pbx1<\/jats:italic>\n            deficiency or\n            <jats:italic>Pbx1-d<\/jats:italic>\n            overexpression reduced the number, stability, and suppressive activity of T\n            <jats:sub>reg<\/jats:sub>\n            cells, which increased murine responses to immunization and autoimmune induction. Mechanistically,\n            <jats:italic>Pbx1<\/jats:italic>\n            deficiency altered the expression of genes implicated in cell cycle and apoptosis in T\n            <jats:sub>reg<\/jats:sub>\n            cells. Intriguingly,\n            <jats:italic>Rtkn2<\/jats:italic>\n            , a Rho-GTPase previously associated with T\n            <jats:sub>reg<\/jats:sub>\n            homeostasis, was directly transactivated by Pbx1. Our results suggest that the maintenance of T\n            <jats:sub>reg<\/jats:sub>\n            cell homeostasis and stability by\n            <jats:italic>Pbx1<\/jats:italic>\n            through cell cycle progression prevent the expansion of inflammatory T cells that otherwise exacerbates lupus progression in the hosts.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adi4310","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T18:00:12Z","timestamp":1711562412000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Lupus susceptibility gene\n            <i>Pbx1<\/i>\n            controls the development, stability, and function of regulatory T cells via\n            <i>Rtkn2<\/i>\n            expression"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-9087","authenticated-orcid":true,"given":"Seung-Chul","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuk Pheel","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-6863","authenticated-orcid":true,"given":"Tracoyia","family":"Roach","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1234-8180","authenticated-orcid":true,"given":"Damian","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2634-144X","authenticated-orcid":true,"given":"Amanda","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojgan","family":"Zadeh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, 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