Abstract
<b>Introduction:</b> Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. <b>Aim/Methods:</b> Lymph node sampling was performed through endobronchial ultrasound (EBUS) bronchoscopy. We aimed to investigate lymphocyte expression of PD-1/PD-L1 axis and CD4/CD8 in mediastinal lymph nodes of patients with IPF and lung cancer. These parameters were also measured in mediastinal lymph nodes of mice at different time points (day 3, day 7, day 14) following bleomycin-injury. <b>Results:</b> Thirty two patients (n=32) were included in the study (IPF: n=13, lung cancer: n=10, concomitant IPF and lung cancer: n=9). Median PD-1% expression was significantly higher in lymphocytes of patients with IPF compared to lung cancer (2.0,95% CI:0.5 to 3.0, vs. 0.0, 95% CI:0.0 to 0.8, p=0.006). Median PD-L1% expression was significantly lower in lymphocytes of patients with IPF compared to lung cancer (0.0,95% CI:0.0 to 0.5, vs. 1.5, 95% CI:0.0 to 2.5, p=0.04). Median CD4/CD8 ratio was significantly higher in mediastinal lymph nodes of patients with IPF compared to patients with lung cancer (1.9, 95% CI:1.2 to 2.6, vs. 0.9, 95% CI:0.7 to 1.3, p=0.0007). Our clinical findings were further corroborated in the experimental model, as CD4+ T cells with high expression of PD-1 promoted fibroblast-to-myofibroblast differentiation. <b>Conclusion:</b> Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles of lymphocyte subpopulations than patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis.
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