26/02/2024
An integrative mathematical model of thymocyte dynamics in human was developed to predict thymic function depending on age in both normal and pathological conditions of the thymus, as well as therapeutic interventions. The model incorporates mechanistic features of thymocyte homeostasis as well as spatial constraints of the thymus and considerations of age-dependent involution. We found thymic function to be most impacted by the egress, proliferation, differentiation and death rates of those thymocytes which are most differentiated. Model predictions also showed that the clinically observed decrease in relapse risk with age, in multiple sclerosis patients who would have discontinued fingolimod therapy, can be explained mechanistically by decreased thymic output with age.
