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Enhanced apoptosis due to increased TCR signaling in T-KO iNKT thymocytes of developmental stages 2 and 3 shows that Kidins220 down-regulates TCR signaling at these stages. scRNA-seq \u2009indicated that the transcription factor Aiolos is down-regulated in Kidins220-deficient iNKT cells. Analysis of an Aiolos KO demonstrated that Aiolos is a downstream effector of Kidins220 during iNKT cell development. In the periphery, T-KO iNKT cells show reduced TCR signaling upon stimulation with \u03b1-galactosylceramide, suggesting that Kidins220 promotes TCR signaling in peripheral iNKT cells. Thus, Kidins220 reduces or promotes signaling dependent on the iNKT cell developmental stage.<\/jats:p>","DOI":"10.1126\/sciadv.adj2802","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T17:58:37Z","timestamp":1710525517000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Kidins220 and Aiolos promote thymic iNKT cell development by reducing TCR signals"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1035-2558","authenticated-orcid":true,"given":"Laurenz A.","family":"Herr","sequence":"first","affiliation":[{"name":"Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany."},{"name":"Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany."},{"name":"Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8226-5584","authenticated-orcid":true,"given":"Gina J.","family":"Fiala","sequence":"additional","affiliation":[{"name":"Signaling Research Centers BIOSS and CIBSS; 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