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Zebl represses TCR signaling, promotes the proliferation of T cell progenitors and is essential for NK1.1^(+) T cell development

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Cellular & Molecular Immunology 2021年第9期18卷 2140-2152页

作者： Jiang Zhang Melanie Wencker Quentin Marliac Aurore Berton Uzma Hasan Raphael Schneider Daphne Laubreton Dylan E.Cherrier Anne-Laure Mathieu Amaury Rey Wenzheng Jiang julie caramel Laurent Genestier Antoine Margais Jacqueline Marvel Yad Ghavi-Helm Thierry Walzer CIRI Centre International de Recherche en InfectiologieUniv LyonInsermU1111Universite Claude Bernard Lyon 1CNRSUMR5308ENS de LyonF-69007 LyonFrance Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina lnstitut de Genomique Fonctionnelle de Lyon CNRS UMR 5242Ecole Normale Superieure de LyonUniversity Claude Bernard Lyon 146 allée d'ltalieF-69364 LyonFrance CRCL Centre de Recherche sur le Cancer de LyonINSERM U1052—CNRS UMR5286Centre Léon BerardUniversity Claude Bernard Lyon 1LyonFrance

T cell development proceeds un der the in fluence of a n etwork of transcription factors(TFs).The precise role of Zeb1,a member of this network,remains ***,we report that Zeb1 expression is induced early during T cell development in CD4^(-)CD8^(-)double-negative(DN)stage 2(DN2).Zeb1 expression was further increased in the CD4^(+)CD8^(+)double-positive(DP)stage before decreasing in more mature T cell *** performed an exhaustive characterization of T cells in Cellophane mice that bear Zeb 7 hypomorphic *** Zebl mutation profoundly affected all thymic subsets,especially DN2 and DP ***1 promoted the survival and proliferation of both cell populations in a cell-intrinsic *** the periphery of Cellophane mice,the number of conventional T cells was near normal,but invariant NKT cells,NK1.1^(+)γδ T cells and Ly49^(+)CD8 T cells were virtually *** suggested that Zebl regulates the development of unconventional T cell types from DP progenitors.A transcriptomic analysis of WT and Cellophane DP cells revealed that Zebl regulated the expression of multiple genes involved in the cell cycle and TCR sign aling,which possibly occurred in cooperation with Tcf1 and *** deed,Cellophane DP cells displayed stron ger signaling than WT DP cells upon TCR engagement in terms of the calcium respons巳phosphorylation events,and expression of early ***,Zebl is a key regulator of the cell cycle and TCR signaling during thymic T cell *** propose that thymocyte selection is perturbed in Zeb7-mutated mice in a way that does not allow the survival of unconventional T cell subsets.

关键词： T cell selection TCR signaling Zebl transcription development

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