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By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. Here we show that mice heterozygous for an\n                    <jats:italic>Ikbkb<\/jats:italic>\n                    gain-of-function mutation develop psoriasis. Doubling the gene dose (\n                    <jats:italic>Ikbkb<\/jats:italic>\n                    <jats:sup>GoF\/GoF<\/jats:sup>\n                    ) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis.\n                    <jats:italic>Ikbkb<\/jats:italic>\n                    <jats:sup>GoF<\/jats:sup>\n                    mice exhibit a selective expansion of Foxp3\u2009+\u2009CD25+ Tregs of which a subset express IL-17. These modified Tregs are enriched in both inflamed tissues, blood and spleen, and their transfer is sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs reveal expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-\u03baB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-45870-3","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T07:02:13Z","timestamp":1711350133000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model"],"prefix":"10.1038","volume":"15","author":[{"given":"Chelisa","family":"Cardinez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3932-3686","authenticated-orcid":false,"given":"Yuwei","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-0009","authenticated-orcid":false,"given":"Kristy","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3352-5578","authenticated-orcid":false,"given":"Ainsley R.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3784-6814","authenticated-orcid":false,"given":"Morgan B.","family":"Downes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4913-0495","authenticated-orcid":false,"given":"Nadia A.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel A.","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lovell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochna","family":"Chand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-5934","authenticated-orcid":false,"given":"Zhi-Ping","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5933-6463","authenticated-orcid":false,"given":"Anselm","family":"Enders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-0298","authenticated-orcid":false,"given":"Carola G.","family":"Vinuesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar","family":"Miraghazadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3331-9363","authenticated-orcid":false,"given":"Matthew C.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"45870_CR1","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/ni904","volume":"4","author":"JD Fontenot","year":"2003","unstructured":"Fontenot, J. 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