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However, the phenotypic and functional features of Tregs in neonatal nonlymphoid organs are not well understood. Our prior work demonstrated that thymus\u2010derived Treg cells entering the neonatal mouse liver enhance immune tolerance and periportal liver maturation. Compared to splenic Treg cells, these hepatic Tregs have faster turnover and superior suppression of na\u00efve T\u2010cell proliferation. To further define this population, we conducted single\u2010cell transcriptomic and immunophenotypic analyses of liver\u2010 and spleen\u2010derived Tregs from neonatal and adult mice. Our analysis revealed a distinct T\u2010box transcription factor\n                    <jats:italic>Tbx21<\/jats:italic>\n                    (T\u2010bet)\n                    <jats:sup>+<\/jats:sup>\n                    effector Treg subset uniquely enriched in the neonatal liver. These cells possess liver\u2010homing properties, clonal expansion of unique T\u2010cell receptor (TCR) repertoires, and heightened suppressive activity. Interleukin\u201027 (IL\u201027) and interferon gamma (IFN\u2010\u03b3), cytokines highly expressed in the neonatal liver, play a critical role in promoting T\u2010bet expression and the acquisition of an ectonucleoside triphosphate diphosphohydrolase 1 (CD39)\n                    <jats:sup>+<\/jats:sup>\n                    C\u2010X\u2010C chemokine receptor type 3 (CXCR3)\n                    <jats:sup>+<\/jats:sup>\n                    double\u2010positive phenotype in Treg cells. Collectively, our findings characterize a liver\u2010specific neonatal T\u2010bet\n                    <jats:sup>+<\/jats:sup>\n                    Treg population shaped by the hepatic microenvironment, highlighting its unique tissue\u2010resident signature and immunoregulatory role.\n                  <\/jats:p>","DOI":"10.1111\/febs.70486","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T06:52:08Z","timestamp":1773125528000},"page":"4704-4723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["T\u2010bet\n                    <sup>+<\/sup>\n                    tissue\u2010resident regulatory T\u00a0cells are enriched in the neonatal mouse liver and promoted by\n                    <scp>IL<\/scp>\n                    \u201027 and\n                    <scp>IFN<\/scp>\n                    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