The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection

Author:

Klein Fabian1ORCID,Mitrovic Mladen2ORCID,Roux Julien34ORCID,Engdahl Corinne1,von Muenchow Lilly1ORCID,Alberti-Servera Llucia1,Fehling Hans Jörg5ORCID,Pelczar Pawel6ORCID,Rolink Antonius1,Tsapogas Panagiotis1ORCID

Affiliation:

1. Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland

2. Immune Regulation, Department of Biomedicine, University of Basel, Basel, Switzerland

3. Bioinformatics Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland

4. Swiss Institute of Bioinformatics, Lausanne, Switzerland

5. Institute of Immunology, University Hospital, Ulm, Germany

6. Center for Transgenic Models, University of Basel, Basel, Switzerland

Abstract

T cell development is critically dependent on successful rearrangement of antigen-receptor chains. At the β-selection checkpoint, only cells with a functional rearrangement continue in development. However, how nonselected T cells proceed in their dead-end fate is not clear. We identified low CD27 expression to mark pre-T cells that have failed to rearrange their β-chain. Expression profiling and single-cell transcriptome clustering identified a developmental trajectory through β-selection and revealed specific expression of the transcription factor Duxbl at a stage of high recombination activity before β-selection. Conditional transgenic expression of Duxbl resulted in a developmental block at the DN3-to-DN4 transition due to reduced proliferation and enhanced apoptosis, whereas RNA silencing of Duxbl led to a decrease in apoptosis. Transcriptome analysis linked Duxbl to elevated expression of the apoptosis-inducing Oas/RNaseL pathway. RNaseL deficiency or sustained Bcl2 expression led to a partial rescue of cells in Duxbl transgenic mice. These findings identify Duxbl as a regulator of β-selection by inducing apoptosis in cells with a nonfunctional rearrangement.

Funder

Swiss National Science Foundation

People Program

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3