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However, even though there is continual thymic involution and regeneration in response to everyday insults like stress and infection, profound thymic damage such as ionizing radiation leads to prolonged T cell lymphopenia for which there is currently no therapeutic treatment. We and others have been focusing in recent years on untangling the cellular and molecular mechanisms underlying endogenous thymic regeneration in the hope of being able to exploit them for clinical benefit. To date, multiple molecular mechanisms have been identified that are centered on several distinct cell axes, including interleukin\u201022 produced by innate lymphoid cells, BMP4 by endothelial cells, and type 2 cytokines from eosinophils, ILCs, and Tregs. Notably, one of the uniting triggers for these pathways of repair centers on the balance of cell death detection. In this review, we will highlight the current state of play with regard to cellular and molecular pathways of regeneration as well as the mechanisms triggering them. 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