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

Area of Science:

• Immunology
• Pulmonology
• Fibrosis Research

Background:

• Upregulation of PD-1 in CD4+ T cells is linked to lung fibrosis via IL-17/STAT3 activation.
• The role of PD-1+ CD4+ T cells in traumatic tracheal stenosis (TS) remains uninvestigated.

Purpose of the Study:

• To explore the involvement of PD-1+ CD4+ T cells in the pathogenesis of traumatic tracheal stenosis (TS).
• To investigate the potential of targeting the PD-1/STAT3 pathway as an immunotherapeutic strategy for TS fibrosis.

Main Methods:

• Analysis of PD-1+ CD4+ T cells, IL-17A, and TGF-β1 in TS patients.
• In vitro co-culture of CD4+ T cells with bronchial fibroblasts and in vivo animal models of TS.
• Treatment with PD-1 and STAT3 inhibitors in vitro and in vivo.

Main Results:

• TS patients exhibited increased PD-1+ CD4+ T cells, IL-17A, and TGF-β1.
• PD-1 and STAT3 inhibition decreased IL-17A and TGF-β1 expression, reduced collagen I synthesis, and ameliorated tracheal fibrosis.
• Evidence confirmed PD-1 modulates STAT3 signaling.

Conclusions:

• PD-1+ CD4+ T cells play a significant role in the development of tracheal fibrosis in TS.
• Targeting the PD-1/STAT3 pathway presents a promising novel immunotherapeutic approach for treating tracheal stenosis.