{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T05:23:35Z","timestamp":1788067415191,"version":"build-2784847793"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Backgroud:<\/jats:bold> 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 <jats:italic>Ganoderma lucidum<\/jats:italic> spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4<jats:sup>+<\/jats:sup> T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) \u03b1 rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased V\u03b114-J\u03b118 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 (pMHC\u2160)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup>Abpob<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>Apoa4<jats:sup>+<\/jats:sup> T cells by mTECs, resulting in enhanced CD4<jats:sup>+<\/jats:sup> T cell output.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS\u2019s immunoregulatory role pave the way for its potential as a T-cell regeneration inducer.<\/jats:p>","DOI":"10.3389\/fphar.2024.1419881","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T04:18:06Z","timestamp":1723781886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Protective effects of Ganoderma lucidum spores on estradiol benzoate-induced TEC apoptosis and compromised double-positive thymocyte development"],"prefix":"10.3389","volume":"15","author":[{"given":"Jihong","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"858","DOI":"10.3389\/fimmu.2020.00858","article-title":"Generation and regeneration of thymic epithelial cells","volume":"11","author":"Alawam","year":"2020","journal-title":"Front. 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