Thymus aging in mice deficient in either EphB2 or EphB3, two master regulators of thymic epithelium development

Abstract

Background: The epithelial microenvironment is involved in thymus aging, but the possible role of EphB receptors that govern the thymic epithelium development has not been investigated. Herein, we study the changes undergone by the thymus of EphB-deficient mice throughout their life. Results: Immune alterations occurring throughout life were more severe in mutant than in wild-type (WT) mice. Mutant thymuses exhibit lower cellularity than WT ones, as well as lower proportions of early thymic progenitors cells and double-positive (CD4 + CD8 +) thymocytes, but higher of double-negative (CD4 − CD8 −) and single-positive (CD4 + CD8 − , CD4 − CD8 +) cells. Throughout life, CD4 + naïve cells decreased particularly in mutant mice. In correlation, memory T cells, largely CD8 + cells, increased. Aged thymic epithelium undergoes changes including appearance of big epithelial free areas, decrease of K8 + K5 − areas, which, however, contain higher proportions of Ly51 + UEA1 − cortical epithelial cells, in correlation with reduced Aire + medullary epithelial cells. Also, aged thymuses particularly those derived from mutant mice exhibited increased collagen IV, fat-storing cells, and connective cells. Conclusions: The absence of EphB accelerates the alterations undergone throughout life by both thymic epithelium and thymocytes, and the proportions of peripheral naïve and memory T cells, all of which are hallmarks of immune aging.

Intrathymic Selection and Defects in the Thymic Epithelial Cell Development

“…These variations in the amount of yielded thymic cells correlated well with changes in the proportions of the most numerous thymocyte subsets, DP cells and TCRαβ hi CD4 + cells (Tables 1 and 2). Whereas RTOCs constituted with 1 × 10 6 thymic stromal cells showed normal proportions of the distinct thymocyte subsets, quite similar to those reported in 2-month-old adult thymi [139], in RTOCs established with lower numbers of cells, there were some alterations in the T-cell maturation (although not statistically significant) consisting in gradual decreased frequencies of DP cells (Table 1) and increased percentages of TCRαβ hi thymocytes, largely TCRαβ hi CD4 + T-cells (Table 2). This altered pattern of T-cell differentiation was particularly evident in grafted RTOCs formed with 0.085 × 10 6 cells, in which the found values were statistically significant as compared to grafted RTOCs formed with 1 × 10 6 stromal cells (Tables 1 and 2).…”

Dosage effects of resveratrol on thymus involution in D‐galactose‐treated mice

“…Thymus aging accelerates at the beginning of puberty, and presents as a vital clinical complication for cancer patients who need cytoablative therapy (Hun et al, 2020). The epithelial microenvironment reported by García-Ceca et al were involved in thymus senescence (Garcia-Ceca et al, 2020). Therefore, reversing the thymus involution will be beneficial to the health of organisms.…”