PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis

Yan Geng, Xue Liu, Jiurong Liang, David M. Habiel, Vrishika Kulur, Ana Lucia Coelho, Nan Deng, Ting Xie, Yizhou Wang, Ningshan Liu, Guanling Huang, Adrianne Kurkciyan, Zhenqiu Liu, Jie Tang, Cory M. Hogaboam, Dianhua Jiang, Paul W. Noble

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unremitting extracellular matrix deposition, leading to a distortion of pulmonary architecture and impaired gas exchange. Fibroblasts from IPF patients acquire an invasive phenotype that is essential for progressive fibrosis. Here, we performed RNA sequencing analysis on invasive and noninvasive fibroblasts and found that the immune checkpoint ligand CD274 (also known as PD-L1) was upregulated on invasive lung fibroblasts and was required for the invasive phenotype of lung fibroblasts, is regulated by p53 and FAK, and drives lung fibrosis in a humanized IPF model in mice. Activating CD274 in IPF fibroblasts promoted invasion in vitro and pulmonary fibrosis in vivo. CD274 knockout in IPF fibroblasts and targeting CD274 by FAK inhibition or CD274-neutralizing antibodies blunted invasion and attenuated fibrosis, suggesting that CD274 may be a novel therapeutic target in IPF.

Original languageEnglish (US)
Article numbere125326
JournalJCI Insight
Volume4
Issue number6
DOIs
StatePublished - Mar 21 2019

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Idiopathic Pulmonary Fibrosis
Fibrosis
Fibroblasts
Lung
RNA Sequence Analysis
Phenotype
Pulmonary Fibrosis
Neutralizing Antibodies
Extracellular Matrix
Gases
Ligands

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Geng, Y., Liu, X., Liang, J., Habiel, D. M., Kulur, V., Coelho, A. L., ... Noble, P. W. (2019). PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis. JCI Insight, 4(6), [e125326]. https://doi.org/10.1172/jci.insight.125326
Geng, Yan ; Liu, Xue ; Liang, Jiurong ; Habiel, David M. ; Kulur, Vrishika ; Coelho, Ana Lucia ; Deng, Nan ; Xie, Ting ; Wang, Yizhou ; Liu, Ningshan ; Huang, Guanling ; Kurkciyan, Adrianne ; Liu, Zhenqiu ; Tang, Jie ; Hogaboam, Cory M. ; Jiang, Dianhua ; Noble, Paul W. / PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis. In: JCI Insight. 2019 ; Vol. 4, No. 6.
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abstract = "Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unremitting extracellular matrix deposition, leading to a distortion of pulmonary architecture and impaired gas exchange. Fibroblasts from IPF patients acquire an invasive phenotype that is essential for progressive fibrosis. Here, we performed RNA sequencing analysis on invasive and noninvasive fibroblasts and found that the immune checkpoint ligand CD274 (also known as PD-L1) was upregulated on invasive lung fibroblasts and was required for the invasive phenotype of lung fibroblasts, is regulated by p53 and FAK, and drives lung fibrosis in a humanized IPF model in mice. Activating CD274 in IPF fibroblasts promoted invasion in vitro and pulmonary fibrosis in vivo. CD274 knockout in IPF fibroblasts and targeting CD274 by FAK inhibition or CD274-neutralizing antibodies blunted invasion and attenuated fibrosis, suggesting that CD274 may be a novel therapeutic target in IPF.",
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Geng, Y, Liu, X, Liang, J, Habiel, DM, Kulur, V, Coelho, AL, Deng, N, Xie, T, Wang, Y, Liu, N, Huang, G, Kurkciyan, A, Liu, Z, Tang, J, Hogaboam, CM, Jiang, D & Noble, PW 2019, 'PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis', JCI Insight, vol. 4, no. 6, e125326. https://doi.org/10.1172/jci.insight.125326

PD-L1 on invasive fibroblasts drives fibrosis in a humanized model of idiopathic pulmonary fibrosis. / Geng, Yan; Liu, Xue; Liang, Jiurong; Habiel, David M.; Kulur, Vrishika; Coelho, Ana Lucia; Deng, Nan; Xie, Ting; Wang, Yizhou; Liu, Ningshan; Huang, Guanling; Kurkciyan, Adrianne; Liu, Zhenqiu; Tang, Jie; Hogaboam, Cory M.; Jiang, Dianhua; Noble, Paul W.

In: JCI Insight, Vol. 4, No. 6, e125326, 21.03.2019.

Research output: Contribution to journalArticle

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AU - Geng, Yan

AU - Liu, Xue

AU - Liang, Jiurong

AU - Habiel, David M.

AU - Kulur, Vrishika

AU - Coelho, Ana Lucia

AU - Deng, Nan

AU - Xie, Ting

AU - Wang, Yizhou

AU - Liu, Ningshan

AU - Huang, Guanling

AU - Kurkciyan, Adrianne

AU - Liu, Zhenqiu

AU - Tang, Jie

AU - Hogaboam, Cory M.

AU - Jiang, Dianhua

AU - Noble, Paul W.

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