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Following TCR activation, intracellular calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) is the most important second messenger, for which the potassium channel K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 is a relevant regulator. Here, we identify K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-\u03baB-mediated K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 upregulation in tTreg progenitors. K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 provided the driving force for sustained Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx that facilitated NF-\u03baB- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 variant that is associated with poor clinical outcomes indicate that K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 also plays a role in human Treg development. Pharmacological modulation of K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K\n                    <jats:sub>2P<\/jats:sub>\n                    18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders.\n                  <\/jats:p>","DOI":"10.1038\/s41422-021-00580-z","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T11:41:27Z","timestamp":1635248487000},"page":"72-88","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["K2P18.1 translates T cell receptor signals into thymic regulatory T cell development"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6332-8650","authenticated-orcid":false,"given":"Tobias","family":"Ruck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Pfeuffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina 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