Mucosal Immunol. 2026 Jul 17:100387. doi: 10.1016/j.mucimm.2026.100387. Online ahead of print.
ABSTRACT
Idiopathic pulmonary fibrosis is a progressive lung disease characterized by the rapid scarring of the lung parenchyma resulting in impaired gas exchange and early mortality. Current treatment options are limited; lung transplantation remains the only definitive treatment. The adaptive immune system has been increasingly evoked as a potential contributor to disease initiation or progression. Using spectral flow cytometry, immunofluorescence imaging, and in-vitro functional assays we studied T cells obtained from explanted lungs and lung draining lymph nodes (HLN) from patients with IPF and non-diseased controls. We found the accumulation of granzyme K producing, hypofunctional CD8+ T cells in the lungs and HLN from IPF compared to controls. We also showed the accumulation of regulatory T cells in both lung and HLN in patients with IPF. CD4+ and CD8+ T cells were found to accumulate around areas of active fibrosis in IPF lung sections. Finally, when exposed to extracellular granzyme K, epithelial cells from human lungs showed increased expression of genes related to fibrosis, proliferation, and inflammation. Together, these show that IPF lungs and lymph nodes are characterized by the accumulation of granzyme K producing T cells and that granzyme K can promote pro-fibrotic effects of lung epithelial cells, providing a potential means whereby T cells might contribute to lung fibrosis.
PMID:42468720 | DOI:10.1016/j.mucimm.2026.100387