Epithelial-immune crosstalk in lung transplant ischemia-reperfusion injury.

Abstract

Purpose of review: This review examines the epithelial-immune crosstalk in lung transplant ischemia-reperfusion injury (IRI). IRI is the mechanism underpinning primary graft dysfunction (PGD), a clinical syndrome that occurs in nearly one-third of lung transplant recipients associated with increased mortality.

Recent findings: The epithelium is constituted by a diverse array of cells with complex contributions to allograft airway homeostasis. IRI disrupts this balance leading epithelial barrier compromise. However, emerging evidence suggests that epithelial cells are central to the propagation of this initial injury. Epithelial stress responses, including glycocalyx shedding and mitochondrial dysfunction, trigger innate immune activation through the release of DAMPs and stress ligands. Resident macrophages, neutrophils, and NK cells interface directly with epithelial-derived signals to drive inflammation and propagate tissue injury. Additionally, adaptive immune cells, particularly cytotoxic and senescent T cells and B cells, contribute to early and late allograft injury. Novel therapeutic strategies aim to preserve epithelial integrity and modulate immune activation.

Summary: Understanding epithelial-immune crosstalk reveals new avenues for mitigating PGD by targeting epithelial pathways and innate immune effector cells. These insights can inform future therapies to improve lung transplant outcomes and mitigate additional allograft injuries.