Neuroimmune Crosstalk in Psoriasis: Mechanisms and Therapeutic Implications

Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation, dermal vascular remodeling, and dense immune cell infiltration. While the conventional immunopathological model emphasizes the IL-23/Th17 axis and aberrant T-cell responses, growing evidence highlights the central role of neuroimmune crosstalk in the initiation, amplification, and persistence of disease. This review systematically dissects the cellular and molecular mechanisms underpinning neuroimmune interactions in psoriasis, focusing on the dynamic interplay between peripheral nerve fibers, keratinocytes, and immune cells. Key neuropeptides—such as calcitonin gene-related peptide (CGRP), substance P (SP), nerve growth factor (NGF), and vasoactive intestinal peptide (VIP)/PACAP—emerge as critical mediators that activate proinflammatory signaling cascades and perpetuate a positive feedback loop involving IL-23, IL-17, and other cytokines. Concurrently, neurotransmitters including norepinephrine (NE), acetylcholine (ACh), and dopamine (DA) modulate dendritic cell activation, Th17 polarization, and epidermal inflammation via adrenergic, cholinergic, and dopaminergic pathways. Importantly, both central and peripheral nervous systems are implicated in neuroinflammatory sensitization, with IL-17 A, IL-1β, and TNF-α disrupting neuronal homeostasis and contributing to pruritus, pain, and stress-induced relapse. We further summarize emerging therapeutic strategies targeting the neuroimmune axis—such as TRPV1 antagonists, botulinum neurotoxins, NK1R inhibitors, and vagus nerve stimulation—which offer promising avenues for personalized and mechanism-based interventions. By reframing psoriasis as a neuroimmune disorder, this review provides new conceptual insights into disease heterogeneity and points toward innovative treatment paradigms.