The nerve injuries attenuate the persistence of psoriatic lesions.

Abstract Background The involvement of the nerve in psoriasis development was suggested by sporadic case reports. Objectives To provide multiple evidence for the nerve in psoriasis development with a retrospective case review, a literature review and a mouse-based experimental experiment. Methods Psoriatic patients who had concomitant nerve injuries and such cases from literatures were reviewed. And, on wild-type mouse level, unilateral denervation surgery was performed on the dorsal skin before and after the induction of psoriasiform dermatitis, respectively. Lesion visual scores were calculated, and biopsies were taken for hematoxylin-eosin (HE) staining, immunofluorescence analysis, and RNA sequencing & bioinformatics analysis before denervation surgery and the 2nd, 4th, 6th, 8th day after the surgery. Results All clinical cases (20/20) showed that local lesions under the control of injured nerves relieved spontaneously or even cleared/spared, and only about 1/3 experienced partial recurrence. Next, mouse psoriasiform experiments demonstrated that unilateral denervation prior to imiquimod application attenuated the enhancement of inflammatory reactions (e.g. adaptive immune response and Th17 cell differentiation pathway) and the induction of ipsilateral psoriasiform dermatitis. On the other hand, unilateral denervation after psoriasiform dermatitis induction promoted the regression of inflammatory reactions (e.g. T cell activation, TNF signaling, and Th17 cell differentiation pathway) and ipsilateral dermatitis recovery. Conclusion Our study based on both retrospective clinical case review and wild-type mouse experiments provides multiple evidence for the involvement of the nerve in psoriasis development. Regulation of immune events, including TNF signaling and Th17 cell differentiation, may be the mechanisms of the nerve in psoriasis.