Kidins220 and Aiolos promote thymic iNKT cell development by reducing TCR signals.
Fiche publication
Date publication
mars 2024
Journal
Science advances
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan, Dr HEIZMANN Beate
Tous les auteurs :
Herr LA, Fiala GJ, Sagar, Schaffer AM, Hummel JF, Zintchenko M, Raute K, Velasco Cárdenas RM, Heizmann B, Ebert K, Fehrenbach K, Janowska I, Chan S, Tanriver Y, Minguet S, Schamel WW
Lien Pubmed
Résumé
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.
Mots clés
Mice, Animals, Natural Killer T-Cells, metabolism, Receptors, Antigen, T-Cell, genetics, Cell Differentiation, Signal Transduction, Gene Expression Regulation, Mice, Knockout, Mice, Inbred C57BL
Référence
Sci Adv. 2024 03 15;10(11):eadj2802