Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors

European Journal of Immunology
Song BaikGraham Anderson

Abstract

Thymic epithelial cells (TECs) provide essential signals for αβT-cell development, and medullary TECs (mTECs) control T-cell tolerance through both negative selection and Foxp3(+) regulatory T (Treg) cell development. Although heterogeneity within the mTEC compartment is well studied, the molecular regulators of specific stages of mTEC development are still poorly understood. Given the importance of the RANK-RANKL axis in thymus medulla formation, we have used RANK Venus reporter mice to analyze the ontogeny of RANK(+) TECs during development and correlated RANK expression with mTEC stem cells defined by SSEA-1. In addition, we have investigated how requirements for the key regulators Foxn1 and Relb map to specific stages of mTEC development. Here, we show SSEA-1(+) mTEC stem cells emerge prior to RANK expression and are present in both nude and Relb(-/-) mice, providing direct evidence that mTEC lineage specification occurs independently of Foxn1 and Relb. In contrast, we show that Relb is necessary for the effective production of downstream RANK(+) mTEC progenitors. Collectively, our work defines stage-specific requirements for critical TEC regulators during medulla development, including the timing of Relb dependency, and pr...Continue Reading

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Citations

Mar 8, 2016·European Journal of Immunology·Nuno L Alves, Ana R Ribeiro
Sep 21, 2016·Nature Immunology·Jennifer Cowan, Avinash Bhandoola
Mar 21, 2017·Nature Reviews. Immunology·Yousuke TakahamaGraham Anderson
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Feb 23, 2017·Annual Review of Immunology·Jakub Abramson, Graham Anderson
Apr 26, 2017·European Journal of Immunology·Fabian BrunkSheena Pinto
Dec 6, 2019·Nature Reviews. Immunology·Noam KadouriJakub Abramson
Jun 7, 2018·Frontiers in Immunology·Brendan J O'SullivanRanjeny Thomas
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May 8, 2018·Science China. Life Sciences·Caiwei Jin, Mingzhao Zhu
Jun 6, 2018·Frontiers in Immunology·Sara Montero-HerradónAgustín G Zapata
Apr 25, 2018·Frontiers in Immunology·Bahar Miraghazadeh, Matthew C Cook
Jan 5, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Junhui LiXiang Xiao
Sep 26, 2020·Frontiers in Immunology·Jastaranpreet SinghJuan Carlos Zúñiga-Pflücker
May 28, 2020·Frontiers in Immunology·Abdullah S AlawamBeth Lucas
Jun 6, 2017·Nature Reviews. Immunology·Shao-Cong Sun
Feb 28, 2018·Frontiers in Immunology·Roberto Perniola
Jan 16, 2021·Seminars in Immunopathology·Yujun DengHongbo Hu

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Prism
GraphPad
FloJo

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