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

Autor:	Herr LA; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany., Fiala GJ; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany., Sagar; Department of Medicine II (Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Schaffer AM; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany., Hummel JF; Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Germany., Zintchenko M; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany., Raute K; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany., Velasco Cárdenas RM; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany., Heizmann B; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR7104, Université de Strasbourg, Illkirch, France., Ebert K; Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Germany., Fehrenbach K; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany., Janowska I; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany., Chan S; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR7104, Université de Strasbourg, Illkirch, France., Tanriver Y; Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Germany.; Department of Medicine IV: Nephrology and Primary Care, Medical Center, University of Freiburg, Freiburg, Germany., Minguet S; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany., Schamel WW; Signaling Research Centers BIOSS and CIBSS; University of Freiburg, Freiburg, Germany.; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.; Centre for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Mar 15; Vol. 10 (11), pp. eadj2802. Date of Electronic Publication: 2024 Mar 15.
DOI:	10.1126/sciadv.adj2802
Abstrakt:	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.
Databáze:	MEDLINE
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