Effects of gender differences on immune senescence mechanisms

Immunosenescence is thought as the main cause of higher incidence of infections and other diseases in aged people. Thymus is the maturation site of developing thymocytes and its size and function decrease during aging , thymic aging is called as thymic involution. Thymic involution causes decrease in naïve T cell output and adaptive immune response. Gender based difference is observed for thymic involution. Thymic cellularity and thymic output were maintained better in women for advancing ages. Incidence of autoimmune diseases is higher in women as a result. In this study, we had six mice experiment groups as letrozole or testosterone treated 3 monts old females for analysis of testosterone and estrogen effects on thymic involution in addition to 7 days old male, 7 days old female, 3 months old male and 3 months old female groups. Hematopoietic stem and progenitor cells were analysed in bone marrow while thymocytes subpopulations, lymphoid tissue inducer (LTi) cells, myeloid derived suppressor cells (MDSC) and regulatory T (Treg) cells were analyzed for thymus. Thymic ACTR2 (Arp2/3 component), FGF7, FGF7RII, IL-7, IL-7R, IL-22 expressions were analyzed. Methylation analysis was made for ARP2 gene. Naive T cell output was analyzed with sjTREC copy number analysis. Numbers of LTi, double negative (DN) thymocytes which are positively correlated with thymic cellularity were significantly higher in 3 months old females while common lymphoid progenitors were significantly higher in 3 months old female bone marrow. FGF7 gene expression was higher in 3 months old females. Cytoskeleton formation related Arp2 gene in 3 months old mice thymus was found as lower than in 7 days old mice. Treg cells which may have negative effects on thymic stroma-thymocyte interactions was higher in 3 months old males. In conclusion, changes in bone marrow cells was correlated with changes in early thymocytes in thymus, gender seems as a determinant of changes in thymic cellularity related markers as FGF7. LTi and Treg cells may be important determinants of differences in thymic involution between genders.