Kidins220 and Aiolos promote thymic iNKT cell development by reducing TCR signals

Abstract: Development of T cells is controlled by the signal strength of the TCR. The scaffold protein kinase D–interacting substrate of 220 kilodalton (Kidins220) binds to the TCR; however, its role in T cell development was unknown. Here, we show that T cell–specific Kidins220 knockout (T-KO) mice have strongly reduced invariant natural killer T (iNKT) cell numbers and modest decreases in conventional T cells. 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  indicated 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 α-galactosylceramide, suggesting that Kidins220 promotes TCR signaling in peripheral iNKT cells. Thus, Kidins220 reduces or promotes signaling dependent on the iNKT cell developmental stage

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Science Advances. - 10, 11 (2024) , eadj2802, ISSN: 2375-2548

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2024
• Creator: Herr, Laurenz A. ; Fiala, Gina Jasmin ; Sagar ; Schaffer, Anna-Maria ; Hummel, Jonas Florian ; Zintchenko, Marina ; Raute, Katrin ; Velasco Cárdenas, Rubí Misol-Há ; Heizmann, Beate ; Ebert, Karolina ; Fehrenbach, Kerstin ; Janowska, Iga ; Chan, Susan ; Tanriver, Yakup ; Minguet, Susana ; Schamel, Wolfgang

Further information

• DOI: 10.1126/sciadv.adj2802
• URN: urn:nbn:de:bsz:25-freidok-2463351
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:42 PM CET