Breaking with convention: the role of lymphocytes in IPF

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease characterised by excessive extracellular matrix deposition, leading to respiratory failure. While the exact aetiology of IPF remains unclear, growing evidence suggests that immune dysregulation plays a pivotal role in its pathogenesis. Recent research highlights the involvement of conventional (CD4+, CD8+ T cells as well as B cells), and unconventional T cell subsets, including natural killer T cells and mucosal-associated invariant T cells in fibrotic lung disease. Unconventional T cell subsets are known for their rapid response to stress signals, antigen-independent activation and involvement in tissue homeostasis and repair. Their potential to modulate fibrosis through interactions with fibroblasts, macrophages and epithelial cells positions them as key players in lung injury and repair mechanisms. Methods: This review explores the current knowledge of both conventional and unconventional lymphocytes in IPF, examining their contributions to fibrosis development and their potential as therapeutic targets. Conclusions: By elucidating their functions and interactions within the lung microenvironment, we provide insights into novel immunomodulatory strategies for IPF treatment.