The thymus is one of the most crucial immunological organs, undergoing visible age-related shrinkage. Thymic epithelial cells (TECs) play a vital role in maintaining the normal function of the thymus, and their degeneration is the primary cause of age-induced thymic devolution. Thymosin β4 (Tβ4) serves as a significant important G-actin sequestering peptide. The objective of this study was to explore whether Tβ4 influences thymocyte differentiation by regulating the cytoskeletal rearrangement and mitochondrial transfer of TECs. A combination of H&E staining, immunofluorescence, transmission electron microscopy, RT-qPCR, flow cytometry, cytoskeletal immunolabeling, and mitochondrial immunolabeling were employed to observe the effects of Tβ4 on TECs’ skeleton rearrangement, mitochondrial transfer, and thymocyte differentiation. The study revealed that the Tβ4 primarily regulates the formation of microfilaments and the mitochondrial transfer of TECs, along with the formation and maturation of double-negative cells (CD4⁻CD8⁻) and CD4 single-positive cells (CD3⁺TCRβ⁺CD4⁺CD8⁻) thymocytes. This study suggests that Tβ4 plays a crucial role in thymocyte differentiation by influencing the cytoskeletal rearrangement and mitochondrial transfer of TECs. These effects may be associated with Tβ4’s impact on the aggregation of F-actin. This finding opens up new avenues for research in the field of immune aging.

The thymus is a central immune organ for T cell development and plays an extremely important role in immune and aging. The unique physiological processes that occur in women, such as the menstrual cycle, pregnancy, and menopause, contribute to sexual dimorphism in thymic immunity. Thymic epithelial cells (TECs) are key stromal cells that affect thymus development and degeneration. Interestingly, TECs in women have stronger proliferation potentiality and ability for output of T cells than those in men. In comparison to men, women exhibit higher susceptibility to autoimmune disease, which can be attributed to lower AIRE expression in the female thymus, which is influenced by fluctuating hormone levels. In this review, we summarize the principles of female thymus regulation by hormones, particularly the influence of female sex hormones in the development and function of TECs, as well as the underlying mechanisms, with the aim of providing new ideas and strategies to inhibit or slow down female thymus degeneration.

Background: To predict the mechanism of Tunneling nanotubes (TNTs) formation promoted by Epimedin C based on network pharmacology. Methods: The targets of Epimedin C were obtained through the PubChem, Pharm Mapper, Swiss Target Prediction and UniProt databases. Using the Genome Annotation Database Platform (GeneCards) database, the targets of TNTs were identified. The common targets were identified after intersection, and the STRING database was applied to construct a Protein-Protein Interaction (PPI) Network. The DAVID database was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: Through network pharmacology, 11 key targets including ALB, IGF1, BMP2, ACHE, MMP2, LCN2, EGFR, CDK2, SRC, ANXA5, and BMP7 were screened. The GO analysis results involved signaling pathways such as the positive regulation of vascular smooth muscle cell proliferation, positive regulation of osteoblast differentiation, and epithelial to mesenchymal transition. The KEGG results were related to endocrine, bladder cancer, EGFR tyrosine kinase inhibitors of drug resistance, FoxO and other signaling pathways. Conclusions: Epimedin C may promote the generation of TNTs through the endocrine and EGFR tyrosine kinase inhibitor resistance signaling pathways. The findings of this study provide a theoretical basis for further investigation into the mechanism by which Epimedin C promotes TNTs generation.