IL-7 promoted the development of thymic DN3 cells in aged mice via DNA demethylation of Bcl2 and c-Myc genes. (July 2022)

• Record Type: Journal Article
• Authors: Han, Jiangyuan; Ma, Yanlin; Lv, Wei; Wang, Juan; Wu, Yu; Niu, Hongxia; Mi, Youjun; Li, Fei; Zhu, Bingdong
• Is Part Of: Molecular immunology. Volume 147(2022)
• Page Start: 21
• Page End: 29
• Publication Date: 2022-07
• Subjects: IL-7 -- Ageing -- DNA demethylation -- DN3 cells -- Bcl2 -- c-Myc; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.04.013
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: IL-7 promotes the development of thymic double negative (DN) T cells during β-selection, which might contribute to the remission of aging-associated thymic involution. Methylation levels of CpG sites is correlated with aging and modulates the development. To determine the involvement of DNA methylation/demethylation instructed by IL-7 signaling during the expansion of double negative (DN) T cells, the aged mice were treated with recombinant Adeno-Associated Virus 2-mediated IL-7 (rAAV2-IL-7) and the DNA methylation/demethylation modifications in this process were analyzed. The results showed that rAAV2-IL-7 increased the number of thymocytes, especially the DN3 thymocytes during β-selection in aged mice. With aging, the methylation levels of Bcl2 and c-Myc promoter regions were increased in DN3 cells. Following rAAV2-IL-7 treatment, DNA methyltransferase Dnmt3a and Dnmt3b decreased, DNA demethylation factors TET2 and TET3 increased, and the methylation levels of Bcl2 and c-Myc in DN3 cells were reduced during DN3 stage in aged mice, consequently, resulting in the upregulation of Bcl2 and c-Myc and the larger increase of DN3 cells in thymus. In conclusion, these findings showed that Bcl2 and c-Myc genes of DN3 cells had an increased DNA methylation levels in aged mice compared to the young, and the hypermethylation in aged mice could be restored following rAAV2-IL-7 treatment. Highlights: rAAV2-IL-7 increased the number of thymocytes, especially the DN3 thymocytes during β-selection in aged mice. Ageing induced hypermethylation of Bcl2 and c-Myc, rAAV2-IL-7 decreased the corresponding methylation levels. rAAV2-IL-7 increased the expression of Bcl2 and c-Myc by DNA demethylation in DN3 cells of aged mice. The accurate reveals of regulation mechanism at DNA level are helpful to apply IL-7 to alleviate immunosenescence in ageing.