Restoring thymic function: Then and now.

Thymic vulnerability, a leading cause of defective immunity, was discovered decades ago. To date, several strategies have been investigated to unveil any immunorestorative capacities they might confer. Studies exploiting castration, transplantation, adoptive cell therapies, hormones/growth factors, and cytokines have demonstrated enhanced in vitro and in vivo thymopoiesis, albeit with clinical restrictions. In this review, we will dissect the thymus on a physiological and pathological level and discuss the pros and cons of several strategies esteemed thymotrophic from a pre-clinical perspective. Finally, we will shed light on interleukin (IL)-21, a pharmacologically-promising cytokine with a significant thymotrophic nature, and elaborate on its potential clinical efficacy and safety in immune-deficient subjects.