Differential expression of PD-1/PD-L1 axis in mediastinal lymph nodes of experimental and human lung fibrosis

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>&nbsp;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.&nbsp;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&nbsp;indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis.