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Melatonin Attenuates Imiquimod-Induced Psoriasis-Like Inflammation and Restores the Th17/Treg Immune Balance

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Abstract

Psoriasis is a common immune-mediated skin disease characterized by abnormally reactive inflammation and epidermal hyperplasia. Previous studies have shown melatonin (MLT) has powerful anti-inflammatory effects. The mechanisms that MLT regulates psoriasis-associated skin inflammation remain unclear. Here, in imiquimod-induced psoriasis-like mice, MLT supplementation reduced skin inflammation and corrected the Th17/Treg cell imbalance. Network pharmacology and proteome sequencing analyses revealed that MLT attenuates the inflammatory response in the skin of psoriatic mice by inhibiting the PI3K/Akt signaling pathway. Overall, the data suggest that MLT has a protective effect against psoriasis-like inflammation.

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Availability of Data and Materials

The data that support the findings of this study are available on request from the corresponding author, HY, upon reasonable request.

Abbreviations

IMQ:

Imiquimod

MLT:

Melatonin

MTX:

Methotrexate

RT-qPCR:

Real-time quantitative PCR

Ki67:

Antigen KI67

Th:

T helper type

Treg:

Regulatory T cell

PI3K:

Phosphatidylinositol 3-kinase

Akt:

Protein kinase B

CON:

Control

PS:

Psoriasis

MLTL:

Low-dose of melatonin

MLTH:

High-dose of melatonin

LY294002:

PI3k/Akt inhibitor

H&E:

Hematoxylin and eosin

PASI:

Psoriasis severity index

PBS:

Phosphate-buffered saline

KEGG:

Kyoto Encyclopedia of Genes and Genomes

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Funding

This study was supported by the Natural Science Foundation of Chongqing Municipality (no. CSTB2023NSCQ-MSX0168 to HY), the joint project of Chongqing Municipal Health Commission and Chongqing Municipal Science and Technology Bureau (No. 2020MSXM070 to HY), the second batch of Class A reserve talents of the Children’s Hospital Affiliated to Chongqing Medical University (No. RC05036 to HY), and the program for Youth Innovation in Future Medicine, Chongqing Medical University (W0177 to XL).

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Author notes

  1. **aoyan Luo and Huan Yang contributed equally to this study.

Authors and Affiliations

  1. Department of Dermatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, 136 Zhongshan 2nd Road, Yuzhong District, 400014, Chongqing, China

    Zhanting Shen, **qiu Jiang, **aoying Zhou, Qingqing Tan, Jiangshan Pi, Hua Wang, Huan Yang & **aoyan Luo

  2. Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China

    Zhanting Shen, **qiu Jiang, **aoying Zhou, Qingqing Tan, Shi Yan, Xuege Wu, Jiangshan Pi, Hua Wang, Huan Yang & **aoyan Luo

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  1. Zhanting Shen
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Contributions

Zhanting Shen: formal analysis, methodology, validation, visualization, and writing—original draft. **qiu Jiang: methodology. **aoying Zhou: methodology. Qingqing Tan: methodology. Shi Yan: methodology. Xuege Wu: methodology. Jiangshan Pi: methodology. Hua Wang: conceptualization, supervision, and writing—review and editing. Huan Yang: conceptualization, formal analysis, funding acquisition, investigation, project administration, supervision, visualization, writing—original draft, and writing—review and editing. **aoyan Luo: conceptualization, funding acquisition, investigation, supervision, and writing—review and editing.

Corresponding author

Correspondence to **aoyan Luo.

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Study procedures were performed in accordance with the Declaration of Helsinki ethical principles for medical research involving human subjects. This study was approved by the Institutional Ethics Committee of Children’s Hospital of Chongqing Medical University (No. 2023388). Informed consent was obtained from all participants before study inclusion.

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Shen, Z., Jiang, J., Zhou, X. et al. Melatonin Attenuates Imiquimod-Induced Psoriasis-Like Inflammation and Restores the Th17/Treg Immune Balance. Inflammation (2024). https://doi.org/10.1007/s10753-024-02023-4

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