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Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes

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Abstract

Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.

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Data availability

The datasets analyzed during the current study are available in the GEO repository. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse121212 and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse53552.

Abbreviations

BTX-A:

Botulinum toxin A

CGRP:

Calcitonin gene-related peptide

DEG:

Differential expression genes

DRG:

Dorsal root ganglion

ELISA:

Enzyme linked immunosorbent assay

FC:

Fold change

GEO:

Gene Expression Omnibus

HE:

Hematoxylin–eosin staining

IF:

Immunofluorescence

IFN:

Interferon

IHC:

Immunohistochemistry

IL:

Interleukin

IMQ:

Imiquimod

NS:

Normal saline

PASI:

Psoriasis Area Severity Index

PGP9.5:

Protein gene product 9.5

qRT-PCR:

Real-Time Quantitative Reverse Transcription PCR

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81930089).

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Author notes

  1. Si-Qi Chen, Xue-Yan Chen and Ying-Zhe Cui contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jiefang Road, Hangzhou, China

    Si-Qi Chen, Xue-Yan Chen, Ying-Zhe Cui, Bing-Xi Yan, Yuan Zhou, Zhao-Yuan Wang, Fan Xu, Yan-Zhou Huang, Yu-Xin Zheng & Xiao-Yong Man

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  1. Si-Qi Chen
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Contributions

Conceptualization was performed by X-YM and S-QC. Data curation and formal analysis and writing were performed by S-QC, X-YC and Y-ZC. Supervision and validation were performed by YZ, B-XY and Z-YW. Review and editing were performed by FX, Y-ZH and Y-XZ.

Corresponding author

Correspondence to Xiao-Yong Man.

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The authors have no relevant financial or non-financial interests to disclose.

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The study was approved by the Ethics Committee of the Second Affiliated Hospital, Zhejiang University School of Medicine. All animal experiments were performed in accordance with protocols approved by the Animal Care and Use Committee.

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Chen, SQ., Chen, XY., Cui, YZ. et al. Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Cell. Mol. Life Sci. 79, 267 (2022). https://doi.org/10.1007/s00018-022-04299-x

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