Mesenchymal stromal cells ameliorate systemic sclerosis-interstitial lung disease via PD-1/PD-L1 signalling axis.
[OBJECTIVE] Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by progressive pulmonary fibrosis.
APA
Chen Y, Zhu H, et al. (2026). Mesenchymal stromal cells ameliorate systemic sclerosis-interstitial lung disease via PD-1/PD-L1 signalling axis.. RMD open, 12(1). https://doi.org/10.1136/rmdopen-2025-006324
MLA
Chen Y, et al.. "Mesenchymal stromal cells ameliorate systemic sclerosis-interstitial lung disease via PD-1/PD-L1 signalling axis.." RMD open, vol. 12, no. 1, 2026.
PMID
41494735
Abstract
[OBJECTIVE] Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by progressive pulmonary fibrosis. This study aimed to investigate the role of programmed death-1 (PD-1)-expressing T cells in SSc-ILD pathogenesis and evaluate the therapeutic potential and mechanism of mesenchymal stromal cells (MSCs) in mitigating fibrosis.
[METHODS] PD-1 expression in T cells from 30 patients with SSc (including SSc-ILD and SSc-non-ILD (nILD) subgroups) and 15 healthy controls (HCs) was analysed via flow cytometry. A bleomycin (BLM)-induced SSc-ILD mouse model was established to evaluate the effects of MSCs in the treatment of lung collagen deposition and inflammation in SSc-ILD. MSCs were administered intravenously to BLM-treated mice, with programmed death-ligand 1 (PD-L1) knockdown (using small interfering RNA targeting PD-L1, siPD-L1) used to explore the mechanism of MSCs on PD-1/PD-L1 pathway. The effects of MSCs on CD4PD-1 T cell proliferation and apoptosis were evaluated by in vitro co-culture experiment.
[RESULTS] PD-1 expression was significantly elevated in CD3 and CD4 T cells of patients with SSc-ILD compared with HCs and SSc-nILD subgroups. In BLM-induced mice, CD4PD-1 T cells in the lung tissues increased progressively, which was correlated with the severity of lung fibrosis. CD4PD-1 T cells directly stimulated fibroblasts to upregulate the expression of collagen and transforming growth factor β1. Treatment with MSCs reduced pulmonary inflammation, fibrosis and PD-1 T cell frequencies in lung tissues of BLM-induced mice. This therapeutic effect was PD-L1-dependent, as it was mediated by the MSC-induced suppression.
[CONCLUSION] CD4PD-1 T cells drive fibrosis in SSc-ILD, and MSCs ameliorate disease by suppressing PD-1 T cells through PD-L1-mediated mechanisms. These findings highlight PD-1 as a therapeutic target and support the clinical investigation of MSC-based interventions for SSc-ILD.
[METHODS] PD-1 expression in T cells from 30 patients with SSc (including SSc-ILD and SSc-non-ILD (nILD) subgroups) and 15 healthy controls (HCs) was analysed via flow cytometry. A bleomycin (BLM)-induced SSc-ILD mouse model was established to evaluate the effects of MSCs in the treatment of lung collagen deposition and inflammation in SSc-ILD. MSCs were administered intravenously to BLM-treated mice, with programmed death-ligand 1 (PD-L1) knockdown (using small interfering RNA targeting PD-L1, siPD-L1) used to explore the mechanism of MSCs on PD-1/PD-L1 pathway. The effects of MSCs on CD4PD-1 T cell proliferation and apoptosis were evaluated by in vitro co-culture experiment.
[RESULTS] PD-1 expression was significantly elevated in CD3 and CD4 T cells of patients with SSc-ILD compared with HCs and SSc-nILD subgroups. In BLM-induced mice, CD4PD-1 T cells in the lung tissues increased progressively, which was correlated with the severity of lung fibrosis. CD4PD-1 T cells directly stimulated fibroblasts to upregulate the expression of collagen and transforming growth factor β1. Treatment with MSCs reduced pulmonary inflammation, fibrosis and PD-1 T cell frequencies in lung tissues of BLM-induced mice. This therapeutic effect was PD-L1-dependent, as it was mediated by the MSC-induced suppression.
[CONCLUSION] CD4PD-1 T cells drive fibrosis in SSc-ILD, and MSCs ameliorate disease by suppressing PD-1 T cells through PD-L1-mediated mechanisms. These findings highlight PD-1 as a therapeutic target and support the clinical investigation of MSC-based interventions for SSc-ILD.
MeSH Terms
Scleroderma, Systemic; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Animals; Humans; Lung Diseases, Interstitial; Mice; Signal Transduction; Mesenchymal Stem Cells; Disease Models, Animal; Mesenchymal Stem Cell Transplantation; Female; Male; Middle Aged; Bleomycin; Adult; Apoptosis; Cell Proliferation
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