Accumulation of mucosal and lymphoid hypo-functional granzyme K producing CD8+ effector memory T cells in idiopathic pulmonary fibrosis
- 1Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- 2Immunology, University of Pittsburgh, Pittsburgh, PA, USA
- 3Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
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.
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BibTeX
@article{okereke2026accumulation,
title = {{Accumulation of mucosal and lymphoid hypo-functional granzyme K producing CD8+ effector memory T cells in idiopathic pulmonary fibrosis}},
author = {Jetina Okereke and Andrew Craig and Michelle Rojas and Blake Degioanni and Allyson Lieberman and John Sembrat and John Evankovich and William Bain and Harinath Bahudhanapati and Daniel J. Kass and Jonathan K. Alder and Mark E. Snyder},
journal = {Mucosal immunology},
year = {2026},
month = jul,
doi = {10.1016/j.mucimm.2026.100387},
url = {https://doi.org/10.1016/j.mucimm.2026.100387},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Accumulation of mucosal and lymphoid hypo-functional granzyme K producing CD8+ effector memory T cells in idiopathic pulmonary fibrosis
AU - Jetina Okereke
AU - Andrew Craig
AU - Michelle Rojas
AU - Blake Degioanni
AU - Allyson Lieberman
AU - John Sembrat
AU - John Evankovich
AU - William Bain
AU - Harinath Bahudhanapati
AU - Daniel J. Kass
AU - Jonathan K. Alder
AU - Mark E. Snyder
PY - 2026
DA - 2026/07/17
JO - Mucosal immunology
DO - 10.1016/j.mucimm.2026.100387
UR - https://doi.org/10.1016/j.mucimm.2026.100387
AB - 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.
SN - 1933-0219
SN - 1935-3456
ER -