Downregulation of the PD-1/PD-Ls pathway in peripheral cells correlates with asbestosis severity

Our plain-English summary of Downregulation of the PD-1/PD-Ls pathway in peripheral cells correlates with asbestosis severity, by M. Qiu, Y. Chen, Q. Ye (BMC Pulmonary Medicine, 2021).

The study

• Authors: M. Qiu, Y. Chen, Q. Ye
• Journal: BMC Pulmonary Medicine
• Published: 2021;21(1):175
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Asbestosis and silicosis are characterized by diffuse or nodular interstitial lung fibrosis resulting from exposure to asbestos or silica dust, respectively. This study was designed to detect programmed cell death protein (PD-1)/programmed death ligands (PD-Ls) expression in patients with asbestosis and silicosis and to explore the possible clinical significance of PD-1/PD-Ls expression in patients with the two diseases.

Methods: Thirty patients with asbestosis, 23 patients with silicosis and 25 healthy controls were consecutively recruited and provided informed consent to participate in the study. Clinical data were collected from patients' clinical charts. PD-1/PD-Ls expression in peripheral blood (PB) was detected using flow cytometry.

Results: PD-1 was expressed at significantly lower levels on CD4+ or CD8+ peripheral T cells from patients with asbestosis and silicosis than on cells from healthy controls. Similarly, significantly lower PD-L1 and PD-L2 expression was detected on CD14+ monocytes from patients with asbestosis and silicosis than on cells from healthy controls. In addition, no significant differences in PD-1, PD-L1 and PD-L2 expression were observed between the asbestosis and silicosis groups. Moreover, the proportions of PD-1+ CD4+ T cells and PD-1+ CD8+ T cells in patients with asbestosis were positively correlated with the percentage of forced vital capacity predicted.

Conclusions: Decreased PD-1 expression on CD4+ T or CD8+ T cells in PB was positively correlated with the asbestosis severity, implying that pulmonary fibrosis development in patients with asbestosis was positively correlated with the downregulation of the PD-1/PD-Ls pathway.

In plain English

The authors compared blood from 30 patients with asbestosis, 23 with silicosis and 25 healthy controls at a Beijing hospital. The asbestosis patients had been exposed to chrysotile dust in asbestos product manufacturing. Using flow cytometry, they measured PD-1, a protein that restrains T-cell activation, and its partners PD-L1 and PD-L2. The mean share of CD4+ T cells carrying PD-1 was 7.753% with asbestosis and 6.676% with silicosis, versus 11.790% in controls. PD-1 was similarly lower on CD8+ T cells, as were PD-L1 and PD-L2 on monocytes. The asbestosis and silicosis groups did not differ significantly in PD-1, PD-L1 or PD-L2 expression. In asbestosis patients, higher PD-1 proportions went with higher forced vital capacity as a percentage of predicted (r = 0.591 for CD4+, 0.507 for CD8+ T cells). No correlation was found with diffusing capacity or total lung capacity, nor significant differences across CT stages. The authors concluded this implied a link between lung fibrosis and pathway downregulation. They noted controls were younger than asbestosis patients, only blood was tested, and no causal relationship was shown.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional laboratory comparison of consecutively recruited patients and healthy controls; immune markers in peripheral blood were measured by flow cytometry
• Who was studied: 30 patients with asbestosis, 23 patients with silicosis and 25 healthy controls (people having routine health examinations who showed no evidence of disease). Patients were recruited at the Department of Occupational Medicine and Toxicology, Beijing Chao-Yang Hospital, China. Recruitment dates are not given. Mean age was 71.3 years in the asbestosis group, 52.9 years in the silicosis group and 46.8 years in the controls.
• Exposure: Asbestosis patients: occupational exposure to chrysotile dust through asbestos product manufacturing. Silicosis patients: silica dust through stone sculpture manufacturing. No exposure doses are given.
• Main results:
  • Share of CD4+ T cells carrying PD-1: mean 7.753% in the asbestosis group and 6.676% in the silicosis group, compared with 11.790% in healthy controls (P < 0.01)
  • Share of CD8+ T cells carrying PD-1: mean 9.556% in the asbestosis group and 9.132% in the silicosis group, compared with 14.670% in healthy controls (reported as P < 0.05)
  • PD-L1 on CD4+ T cells: mean 0.212% in the asbestosis group and 0.310% in the silicosis group, compared with 0.705% in controls (P < 0.05)
  • PD-L1-positive CD14+ monocytes: mean 0.541% in the asbestosis group and 0.544% in the silicosis group, compared with 1.203% in controls (P < 0.01). PD-L2-positive monocytes: 0.541% (asbestosis), 0.525% (silicosis) and 1.161% (controls) (P < 0.01).
  • No significant difference between the asbestosis and silicosis groups in PD-1 on T cells or in PD-L expression on monocytes
  • In the asbestosis group, the proportions of PD-1-positive CD4+ T cells (r = 0.591, P = 0.008) and PD-1-positive CD8+ T cells (r = 0.507, P = 0.027) were positively correlated with forced vital capacity as a percentage of predicted
  • When asbestosis patients were grouped into CT stages I, II and III, PD-1 expression did not differ significantly among the stages
  • In asbestosis patients, no correlation was found between PD-1 expression and DLCO % predicted or TLC % predicted (the text also lists PaO2 and the composite physiological index)
  • Patients with asbestosis and silicosis showed signs of T-cell activation: lower CD28 and higher HLA-DR expression on T cells
• The authors' conclusion: The authors concluded that lower PD-1 expression on blood T cells, correlated with FVC % predicted, implied a link between pulmonary fibrosis development and downregulation of the PD-1/PD-Ls pathway. They suggested the pathway potentially represents a therapeutic target.
• Limitations the authors state:
  • The control group was significantly younger than the asbestosis group, and the authors could not definitely exclude an effect of age
  • The effects of age could not be definitely excluded
  • Only peripheral blood was tested; expression in the lung was not measured
  • No evidence of a causal relationship between lower lung function and PD-1 expression was obtained

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Silicosis, Interstitial, Fibrosis, Informed Consent, PD-L1, Pulmonary Fibrosis.

Related studies

• The PD-L1/PD-1 pathway promotes dysfunction, but not "exhaustion", in tumor-responding T cells from pleural effusions in lung cancer patients — H. Prado-Garcia, S. Romero-Garcia, et al. (2017)
• Trametinib plus 4-Methylumbelliferone Exhibits Antitumor Effects by ERK Blockade and CD44 Downregulation and Affects PD-1 and PD-L1 in Malignant Pleural Mesothelioma — H. Cho, S. Matsumoto, et al. (2017)
• Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas — C. Combaz-Lair, F. Galateau-Sallé, et al. (2016)
• Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation — A.J. Currie, A. Prosser, et al. (2009)
• Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case-control study — C. Xue, N. Wu, et al. (2017)
• Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) — S. Cedrés, S. Ponce-Aix, et al. (2016)

Browse more research in BMC Pulmonary Medicine, or return to medical research.