Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2.

ABSTRACT: T cell recovery is critical following damage, such as hematopoietic cell transplantation (HCT), with increased reconstitution associated with improved clinical outcomes. Endogenous thymic regeneration, a crucial process for restoring immune competence following cytoreductive therapies such as HCT conditioning, is often delayed, limiting T cell reconstitution. Fully understanding the molecular mechanisms driving regeneration is therefore crucial for uncovering therapeutic targets that can be exploited to enhance thymic function. Here, we identified that CD4+ CD8+ thymocytes rapidly and acutely undergo lytic cell death, specifically pyroptosis, following acute damage caused by ionizing radiation, and release damage-associated molecular patterns (DAMPS) into the thymic microenvironment, inclu

SUBMITTER: Kinsella S 

PROVIDER: S-EPMC12859001 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature