Involvement of PD-1+CD4+ T cells in the development of traumatic tracheal stenosis by regulating the IL-17/STAT3 pathway

Studies have highlighted an upregulation of PD-1 expression in CD4⁺ T cells, which accelerates lung fibrosis by activating the IL-17/STAT3 pathway, leading to IL-17A and TGF-β1 secretion. However, the relation with traumatic tracheal stenosis (TS) remains unexplored. Our analysis found significant increases in PD-1⁺CD4⁺ T cells, IL-17A, and TGF-β1 in the TS patients (n = 10). The cellular model used CD4⁺ T cells co-cultured with bronchial fibroblasts while the animal model used a nylon brush to scrape the damaged tracheal mucosa. Interventions with PD-1 and STAT3 inhibitors both in vivo (n = 5) and in vitro (n = 6) showed decreased expression of TGF-β1 and IL-17A in CD4⁺ T cells, decreased Collagen I synthesis in vivo, and reduced tractal fibrosis in vitro. Furthermore, PD-1's modulation of the STAT3 was evident. This research unveils PD-1⁺CD4⁺ T cells' role in TS, thus suggesting a novel immunotherapeutic strategy to counteract tracheal fibrosis.