Exploring the role of neuro-immune modulation for psoriasis management: a narrative review of existing evidence and future therapies.

BACKGROUND: Psoriasis is a chronic immune-mediated skin disease associated with substantial disease burden and comorbidities including cardiovascular disease, metabolic syndrome, and psychiatric illness. While biologics and small-molecule inhibitors have improved outcomes, disease heterogeneity and the complex drivers of inflammation continue to motivate investigation of complementary therapeutic approaches.

MAJOR FINDINGS: Recent work highlights the role of neuro-immune dysregulation in psoriasis. Stress-induced dysregulation of the hypothalamic-pituitary-adrenal axis and increased sympathetic activity have been shown to amplify cytokine production and impair immune regulation. Peripherally, sensory neurons release substance P and CGRP, promoting dendritic cell activation and sustaining Th17-driven inflammation. In contrast, the cholinergic anti-inflammatory reflex, mediated by vagus and splenic nerves through α7 nicotinic acetylcholine receptor signaling, provides an endogenous mechanism to suppress inflammation. Preclinical studies demonstrate that denervation, neuropeptide receptor blockade, vagus nerve stimulation (VNS), and focused ultrasound (fUS) of the splenic nerve attenuate inflammatory immune cell activation and reduce pro-inflammatory cytokine production. Early clinical studies suggest that non-invasive VNS and splenic fUS are safe, feasible, and may reduce systemic inflammatory activity. Additional emerging strategies include neuropeptide receptor blockade, phototherapy-mediated neuroimmune modulation, and lifestyle interventions targeting stress and systemic inflammation.

CONCLUSION: Psoriasis arises from complex interactions among immune, cutaneous, and neural systems. Growing evidence suggests that neuroimmune pathways may represent therapeutic targets beyond conventional cytokine-directed approaches. While preclinical studies and early clinical investigations support the feasibility of neuromodulatory strategies such as vagus nerve stimulation and splenic focused ultrasound, their efficacy in psoriasis remains to be established. Further mechanistic studies and well-designed clinical trials are needed to define their therapeutic role, optimize treatment parameters, and determine long-term safety and clinical effectiveness.