{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:52Z","timestamp":1785434872725,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,17]]},"group-title":"Immunology","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Department of Veterans Affairs Biomedical Laboratory Research and Development Service","award":["I01BX005142"],"award-info":[{"award-number":["I01BX005142"]}]},{"award":["R56 AI108786"],"award-info":[{"award-number":["R56 AI108786"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Z99 HL999999"],"award-info":[{"award-number":["Z99 HL999999"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Gene expression in regulatory T cells (Tregs) is context-dependent and maintains peripheral immune homeostasis. FOXP3 is lineage defining but not sufficient for Treg function or persistence. To define the cell-intrinsic roles of the FOXP3 paralogs FOXP1 and FOXP4, we generated and studied mice with Treg-specific deletion of\n                  <jats:italic>Foxp1<\/jats:italic>\n                  and\/or\n                  <jats:italic>Foxp4<\/jats:italic>\n                  . FOXP1 and FOXP4 are required to maintain the peripheral Treg pool through enhancing\n                  <jats:italic>Il2ra<\/jats:italic>\n                  transcription, thereby promoting sustained high-level expression of IL-2R\u03b1 and thus of the high-affinity IL-2R\u03b1\u03b2\u03b3 complex. Integrating RNA-seq and ATAC-seq with previously published ChIA-PET and publicly available data, we propose a model of\n                  <jats:italic>Il2ra<\/jats:italic>\n                  transcriptional regulation in which in which FOXP1 and FOXP4 anchor chromatin looping of the\n                  <jats:italic>Il2ra<\/jats:italic>\n                  locus in mature Tregs, augment super-enhancer activity, and drive sustained CD25 expression. Our results reveal a unique role of FOXP1, and to a lesser extent FOXP4, in controlling Treg homeostasis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>\n                    FOXP1 and FOXP4 regulate chromatin architecture at the\n                    <jats:italic>Il2ra<\/jats:italic>\n                    locus, promoting sustained CD25 expression and maintaining the peripheral Treg pool.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.14.718220","type":"posted-content","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:35:21Z","timestamp":1776447321000},"source":"Crossref","is-referenced-by-count":0,"title":["FOXP-stabilization of the\n                  <i>Il2ra<\/i>\n                  super-enhancer structure augments Treg fitness"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5443-5304","authenticated-orcid":false,"given":"Dachuan","family":"Dong","sequence":"first","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA"},{"name":"Department of Medicine, Division of Nephrology, Stanford University, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6470-6155","authenticated-orcid":false,"given":"Lauren E.","family":"Higdon","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA"},{"name":"Department of Medicine, Division of Nephrology, Stanford University, Palo Alto, California, 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