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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1419881

Protective Effects of Ganoderma lucidum Spores on Estradiol Benzoate-Induced TEC Apoptosis and Compromised Double-Positive Thymocyte Development

Provisionally accepted
Jihong Yang Jihong Yang 1*Haitao Pan Haitao Pan 2Mengyao Wang Mengyao Wang 2Anyao Li Anyao Li 1Guoliang Zhang Guoliang Zhang 3Xiaohui Fan Xiaohui Fan 1Zhenhao LI Zhenhao LI 1*
  • 1 Zhejiang University, Hangzhou, China
  • 2 BoYu Intelligent Health Innovation Laboratory, HANG ZHOU, China
  • 3 Zhejiang Shouxiangu Botanical Drug Institute Co., Ltd, Hangzhou, Jiangsu Province, China

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

    Backgroud: Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of Ganoderma lucidum spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive.In this study, a mice model of estradiol benzoate (EB)-induced thymic atrophy was constructed, and the improvement effect of GLS on thymic atrophy was evaluated. Then, we employs multi-omics techniques to elucidate how GLS modulates T cell development amidst EB-induced thymic atrophy in mice.Results: GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4 + T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) α rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased Vα14-Jα18 rearrangement fosters double-positive (DP) to invariant natural killer T (iNKT) cell differentiation, partially contingent on RGLS-mediated restriction of peptide-major histocompatibility complex I (pMHCⅠ)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4 + iNKT cell development. Furthermore, RGLS amplifies interaction between a DP subpopulation, termed DPsel-7, and plasmacytoid dendritic cells (pDCs), likely facilitating the subsequent development of double-negative iNKT1 cells. Lastly, RGLS suppresses EB-induced up-regulation of Abpob and Apoa4, curbing the clearance of CD4 + Abpob + and CD4 + Apoa4 + T cells by mTECs, resulting in enhanced CD4 + T cell output.Discussion: These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS's immunoregulatory role pave the way for its potential as a T-cell regeneration inducer.

    Keywords: Ganoderma lucidum spores1, T cell development2, thymic atrophy3, T cell receptor gene rearrangement4, single-cell RNA sequencing5, Proteomics6

    Received: 30 May 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Yang, Pan, Wang, Li, Zhang, Fan and LI. 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:
    Jihong Yang, Zhejiang University, Hangzhou, China
    Zhenhao LI, Zhejiang University, Hangzhou, China

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