Periostin drives psoriasis progression through the stimulation of cutaneous nerve fibers.

Cutaneous nerve fibers play a significant regulatory role in psoriasis progression, with periostin (POSTN) acting as a key molecule in the neuro-immune-cutaneous axis. Using patient samples, neuronal cultures, and Postn -/- mice, we investigated the role of POSTN through molecular, histological, and transcriptomic analyses. Results demonstrated that POSTN is upregulated in psoriatic epidermis and dermis. Conversely, Postn -/- mice displayed alleviated psoriasis-like symptoms, decreased cutaneous nerve fiber density, and reduced nociceptive dorsal root ganglia (DRG) neurons with impaired neurite complexity. Mechanistically, POSTN promotes axonal growth by activating the PI3K/AKT/mTOR signaling pathway. Furthermore, applying cilengitide gel improved psoriatic skin lesions. Ultimately, this study identifies POSTN as a crucial regulator of cutaneous nerve fiber growth during psoriasis progression, highlighting its promise as a therapeutic target.