Rarefaction of peritubular capillaries (PTC) is a key determinant of chronic kidney disease (CKD) after ischemia-reperfusion injury (IRI), especially in older kidneys. Apoptosis of endothelial cells (EC), whether at the time of IRI or during rarefaction, triggers the release of ApoExo, a novel and immunogenic type of extracellular vesicles characterized by the presence of active 20S proteasome and LG3, a C-terminal fragment of perlecan. Contrary to classical apoptotic bodies, ApoExo induce immunogenic responses that can become maladaptive if dysregulated. These potentially maladaptive immune responses include i) interactions with anti-LG3 antibodies, which are associated with reduced long-term function in kidney transplant recipients (KTR) with delayed graft function (DGF) or acute vascular rejection; ii) intra-renal formation of tertiary lymphoid structures (TLS) that are associated with progressive renal dysfunction and; iii) complement activation that can, in turn, contribute to PTC injury. This research project aims to characterize the contributions of anti-LG3, TLS and complement activation in maladaptive immune responses to ApoExo implicated in progressive renal dysfunction after IRI.