In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-β/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF. Here, SMAD3 is linked to pemphigus foliaceus.