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Intermittent fasting alleviates IMQ-induced psoriasis-like dermatitis via reduced γδT17 and monocytes in mice

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Abstract

Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.

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Acknowledgements

The authors greatly appreciate Ruizhi Zhang (The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China) for revising the language used in this revision.

Funding

Science and Technology Program of Guangzhou (202102080341 to ES), Discipline from School of Basic Medicine of Guangzhou Medical University (JCXKJS2021C11 to ES), Innovation projects of Colleges and Universities in Guangdong from Department of Education of Guangdong Province (2021KTSCX090 to ES), Guangzhou Medical University 2022 Student Innovation Ability Improvement Program (to ES).

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Author notes

  1. Xiangming Chen, Cheng Fu, and Yanling Zheng have contributed equally to this work.

Authors and Affiliations

  1. Sino-French Hoffmann Institute, School of Basic Medical Sciences, The Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China

    Xiangming Chen, Cheng Fu, Yanling Zheng, Xiaomin Li, Yue Liao, Wenting Liang, Yuyang Zhao, Jijun Huang, Ting Huang & Erxia Shen

  2. Shenzhen Children’s Hospital, Shenzhen, China

    Cheng Fu

  3. Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, China

    Yanling Zheng

  4. National Center for STD Control, Chinese Center for Disease Control and Prevention, Nanjing, 200042, Jiangsu, China

    Yu Zheng & Jin Bu

  5. Hospital for Skin Disease (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China

    Jin Bu

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  1. Xiangming Chen
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Contributions

ES, JB and XC conceived the experiments. XC, CF and YLZ performed the study. ES, XC analyzed the data. XL, YL, YZ, WL, YYZ, JH and TH assisted to perform the experiments. XC, CF and YLZ established the psoriasis model of mice. ES, JB, XC, CF and YLZ wrote the paper. All authors review the manuscript and approved the submitted version.

Corresponding authors

Correspondence to Jin Bu or Erxia Shen.

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Ethics statement

This study was conducted in compliance with the Declaration of Helsinki and was approved by the ethics committee of Guangzhou Medical University (Guangzhou, China).

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Figure S1 No difference of epidermis thickness of skin and ear without IMQ

. (A) Representative pictures of H&E-stained sections (left) isolated on day 5 from skin lesions and right ear of AL and IF mice without IMQ application. Statistical analysis (right) of epidermal thickness (μm) of skin and ear. (B) Representative flow plots (right) and the percentage of γδT in CD45+ cells (left) from iLN of AL and IF mice without application with IMQ. iLN, inguinal draining lymph nodes. (C) Representative flow plots (right) and percentage of γδTint in CD45+ cells (left) from skin of AL and IF mice without application with IMQ. The data are representative of three independent experiments (A, n=3-5/group; B and C, n=5/group). Bar=100 μm. *p<0.05, **p<0.01. Figure S2 IF reduces monocytes and macrophages in spleen. (A) Representative flow chats (left) and statistical analysis (right) of the percentage of monocytes including Ly6Chi and Ly6Clow monocytes after mice applicated with or without IMQ for 5 days. (B) The percentage and cell numbers of macrophages from spleen in AL and IF group applicated with or without IMQ for 5 days. (C) The percentage and cell numbers of DC from spleen in AL and IF group applicated with or without IMQ for 5 days. The data are representative of two independent experiments (n=4-5/group).*p<0.05, **p<0.01. Figure S3 IF reduces circulating monocyte through re-entering into the BM via CXCR4. (A-B) CXCR4 expression levels (MFI) expression in Ly6Clow and Ly6Chi monocytes from BM and (C-D) peripheral blood of AL and IF mice with IMQ application for 5 days. BM, bone marrow. The data are representative of three independent experiments (A and B, n=5-8/group; C and D, n=4-5/group).*p<0.05, **p<0.01. Figure S4 Gating strategy. (A-B) Gating strategy for skin and iLN γδT cells and IL-17A production upon stimulation. (C-D) Gating strategy for monocytes, macrophages and DC cells from skin and spleen. (PDF 2050 KB)

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Chen, X., Fu, C., Zheng, Y. et al. Intermittent fasting alleviates IMQ-induced psoriasis-like dermatitis via reduced γδT17 and monocytes in mice. Arch Dermatol Res 316, 176 (2024). https://doi.org/10.1007/s00403-024-02886-5

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