Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1500908
This article is part of the Research Topic Thymus Research and Development: A New Look to the Past, Current Knowledge, and Future Perspectives View all 3 articles

Direct and indirect RANK and CD40 signaling regulate the maintenance of thymic epithelial cell frequency and properties in the adult thymus

Provisionally accepted
Mio Hayama Mio Hayama Hiroto Ishii Hiroto Ishii Maki Miyauchi Maki Miyauchi Masaki Yoshida Masaki Yoshida Naho Hagiwara Naho Hagiwara Wataru Muramtatu Wataru Muramtatu Kano Namiki Kano Namiki Rin Endo Rin Endo Takahisa Miyao Takahisa Miyao Nobuko Akiyama Nobuko Akiyama *Taishin Akiyama Taishin Akiyama *
  • RIKEN Yokohama, Yokohama, Japan

The final, formatted version of the article will be published soon.

    Medullary thymic epithelial cells (mTECs) play a crucial role in suppressing the onset of autoimmunity by eliminating autoreactive T cells and promoting the development of regulatory T cells in the thymus. Although mTECs undergo turnover in adults, the molecular mechanisms behind this process remain unclear. This study describes the direct and indirect roles of receptor activator of NF-κB (RANK) and CD40 signaling in TECs in the adult thymus. Flow cytometric and single-cell RNA-seq (scRNA-seq) analyses suggest that the depletion of both RANK and CD40 signaling inhibits mTEC differentiation from CCL21 + mTEC progenitors to transit-amplifying TECs in the adult thymus. Unexpectedly, this depletion also exerts indirect effects on the gene expression of TEC progenitors and cortical TECs. Additionally, the expression levels of AP-1 genes, which enable the further subdivision of TEC progenitors, are up-regulated following the depletion of RANK and CD40 signaling. Overall, our data propose that RANK and CD40 signaling cooperatively maintain mature mTEC frequency in the adult thymus and sustain the characteristics of TEC progenitors through an indirect mechanism.

    Keywords: thymic epithelial cell (TEC), self-tolerance, TNF receptor (TNFR) family, progenitor, AIRE

    Received: 24 Sep 2024; Accepted: 13 Nov 2024.

    Copyright: © 2024 Hayama, Ishii, Miyauchi, Yoshida, Hagiwara, Muramtatu, Namiki, Endo, Miyao, Akiyama and Akiyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Nobuko Akiyama, RIKEN Yokohama, Yokohama, Japan
    Taishin Akiyama, RIKEN Yokohama, Yokohama, Japan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.