Protective effects of Ganoderma lucidum spores on estradiol benzoate-induced TEC apoptosis and compromised double-positive thymocyte development.

Autor:	Yang J; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.; BoYu Intelligent Health Innovation Laboratory, Hangzhou, Zhejiang, China.; ShouXianGu Botanical Drug Institute, Hangzhou, Zhejiang, China., Pan H; BoYu Intelligent Health Innovation Laboratory, Hangzhou, Zhejiang, China., Wang M; BoYu Intelligent Health Innovation Laboratory, Hangzhou, Zhejiang, China., Li A; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China., Zhang G; ShouXianGu Botanical Drug Institute, Hangzhou, Zhejiang, China., Fan X; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.; National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, Zhejiang, China., Li Z; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.; BoYu Intelligent Health Innovation Laboratory, Hangzhou, Zhejiang, China.; ShouXianGu Botanical Drug Institute, Hangzhou, Zhejiang, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Aug 16; Vol. 15, pp. 1419881. Date of Electronic Publication: 2024 Aug 16 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1419881
Abstrakt:	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. Methods: 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 upregulation 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Yang, Pan, Wang, Li, Zhang, Fan and Li.)
Databáze:	MEDLINE
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