{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:13:59Z","timestamp":1790810039264,"version":"4.1.0"},"reference-count":81,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"75","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:p>\n            Regulatory T cells (T\n            <jats:sub>regs<\/jats:sub>\n            ) in nonlymphoid organs provide critical brakes on inflammation and regulate tissue homeostasis. Although so-called \u201ctissue T\n            <jats:sub>regs<\/jats:sub>\n            \u201d are phenotypically and functionally diverse, serving to optimize their performance and survival, up-regulation of pathways related to circadian rhythms is a feature they share. Yet the diurnal regulation of T\n            <jats:sub>regs<\/jats:sub>\n            and its consequences are controversial and poorly understood. Here, we profiled diurnal variations in visceral adipose tissue (VAT) and splenic T\n            <jats:sub>regs<\/jats:sub>\n            in the presence and absence of core-clock genes. VAT, but not splenic, T\n            <jats:sub>regs<\/jats:sub>\n            up-regulated their cell-intrinsic circadian program and exhibited diurnal variations in their activation and metabolic state. BMAL1 deficiency specifically in T\n            <jats:sub>regs<\/jats:sub>\n            led to constitutive activation and poor oxidative metabolism in VAT, but not splenic, T\n            <jats:sub>regs<\/jats:sub>\n            . Disruption of core-clock components resulted in loss of fitness: BMAL1-deficient VAT T\n            <jats:sub>regs<\/jats:sub>\n            were preferentially lost during competitive transfers and in heterozygous T\n            <jats:sub>reg<\/jats:sub>\n            <jats:sup>\n              <jats:italic>Bmal1<\/jats:italic>\n              \u0394\n            <\/jats:sup>\n            females. After 16 weeks of high-fat diet feeding, VAT inflammation was increased in mice harboring BMAL1-deficient T\n            <jats:sub>regs<\/jats:sub>\n            , and the remaining cells lost the transcriptomic signature of bona fide VAT T\n            <jats:sub>regs<\/jats:sub>\n            . Unexpectedly, VAT T\n            <jats:sub>regs<\/jats:sub>\n            suppressed adipocyte lipolysis, and BMAL1 deficiency specifically in T\n            <jats:sub>regs<\/jats:sub>\n            abrogated the characteristic diurnal variation in adipose tissue lipolysis, resulting in enhanced suppression of lipolysis throughout the day. These findings argue for the importance of the cell-intrinsic clock program in optimizing VAT T\n            <jats:sub>reg<\/jats:sub>\n            function and fitness.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abl7641","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T17:57:28Z","timestamp":1664560648000},"source":"Crossref","is-referenced-by-count":57,"title":["T\n            <sub>regs<\/sub>\n            in visceral adipose tissue up-regulate circadian-clock expression to promote fitness and enforce a diurnal rhythm of lipolysis"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4508-3973","authenticated-orcid":true,"given":"Tianli","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-1911","authenticated-orcid":true,"given":"P. Kent","family":"Langston","sequence":"additional","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-723X","authenticated-orcid":true,"given":"Andr\u00e9s R.","family":"Mu\u00f1oz-Rojas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8075-7251","authenticated-orcid":true,"given":"Teshika","family":"Jayewickreme","sequence":"additional","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-1280","authenticated-orcid":true,"given":"Mitchell A.","family":"Lazar","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."},{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."},{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-6555","authenticated-orcid":true,"given":"Christophe","family":"Benoist","sequence":"additional","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA, USA."},{"name":"Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6110-4626","authenticated-orcid":true,"given":"Diane","family":"Mathis","sequence":"additional","affiliation":[{"name":"Department of Immunology, Harvard Medical School, Boston, MA, USA."},{"name":"Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, MA, 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