{
  "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 CD4 +PD-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, CD4+PD-1+ T cells in the lung tissues increased progressively, which was correlated with the severity of lung fibrosis. CD4+PD-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 CD4 +PD-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.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Yuxuan Chen"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Huimin Zhu"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Jiangsu University, Nanjing, Jiangsu, China"
      ],
      "name": "Yue Zhang"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China"
      ],
      "name": "Mian Liu"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Yingyi Wu"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Shuai Ding"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Dandan Wang"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Lingyun Sun"
    }
  ],
  "title": "Mesenchymal stromal cells ameliorate systemic sclerosis-interstitial lung disease via PD-1/PD-L1 signalling axis",
  "uid": "0b83ca77-ce51-58ed-9cde-199556e868b8"
}