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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:p>\n                    Activated Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T (Treg) cells differentiate into effector Treg (eTreg) cells to maintain peripheral immune homeostasis and tolerance. T cell receptor (TCR)\u2013mediated induction and regulation of store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry (SOCE) is essential for eTreg cell differentiation and function. However, SOCE regulation in Treg cells remains unclear. Here, we show that inositol polyphosphate multikinase (IPMK), which generates inositol tetrakisphosphate and inositol pentakisphosphate, is a pivotal regulator of Treg cell differentiation downstream of TCR signaling. IPMK is highly expressed in TCR-stimulated Treg cells and promotes a TCR-induced Treg cell program. IPMK-deficient Treg cells display aberrant T cell activation and impaired differentiation into ROR\u03b3t\n                    <jats:sup>+<\/jats:sup>\n                    Treg cells and tissue-resident Treg cells. Mechanistically, IPMK controls the generation of higher-order inositol phosphates, thereby promoting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization and Treg cell effector functions. Our findings identify IPMK as a critical regulator of TCR-mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx and highlight the importance of IPMK in Treg cell-mediated immune homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2121520119","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T12:05:06Z","timestamp":1656677106000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Differentiation and homeostasis of effector Treg cells are regulated by inositol polyphosphates modulating Ca\n                    <sup>2+<\/sup>\n                    influx"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7874-139X","authenticated-orcid":false,"given":"Hyungyu","family":"Min","sequence":"first","affiliation":[{"name":"School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-3895","authenticated-orcid":false,"given":"Jinguk","family":"Jeong","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-9414","authenticated-orcid":false,"given":"Seyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-0718","authenticated-orcid":false,"given":"Rho H.","family":"Seong","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 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