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

Medientyp: E-Artikel

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

Beteiligte: Herr, Laurenz A.; Fiala, Gina J.; Sagar; Schaffer, Anna-Maria; Hummel, Jonas F.; Zintchenko, Marina; Raute, Katrin; Velasco Cárdenas, Rubí M.-H.; Heizmann, Beate; Ebert, Karolina; Fehrenbach, Kerstin; Janowska, Iga; Chan, Susan; Tanriver, Yakup; Minguet, Susana; Schamel, Wolfgang W.

Erschienen: American Association for the Advancement of Science (AAAS), 2024

Sprache: Englisch

DOI: 10.1126/sciadv.adj2802

ISSN: 2375-2548

Schlagwörter: Multidisciplinary

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Beschreibung: 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.

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