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Shikonin Controls the Differentiation of CD4+CD25+ Regulatory T Cells by Inhibiting AKT/mTOR Pathway

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Abstract

CD4+CD25+ regulatory T (Treg) cells maintain the function of immune tolerance and the balance of immune cells. Defects in the number and function of Treg cells can induce the development and progression of inflammatory disease. Shikonin, the main active ingredient of Lithospermum, has anti-inflammatory and anti-tumor effects. Shikonin is also an effective drug for the treatment of psoriasis, which is a chronic inflammatory skin disease. However, the underlying mechanism is not yet clear. To evaluate the role of shikonin on the induction of Treg cells, we tested the number and function of Treg cells in vivo and in vitro. Shikonin can effectively promote the differentiation of iTreg cells by inhibiting the AKT/mTOR pathway in vitro. Moreover, in vivo, intragastrically administered shikonin effectively improved lesions in mice with imiquimod-induced psoriasis and increased the number of iTreg cells in the spleen and their secretion. Shikonin significantly increases the expression of Foxp3mRNA in skin of the psorisic mice. Therefore, we expect that shikonin can prevent the development of inflammation and treat psoriasis by regulating iTreg cells. Novel ideas for the treatment of psoriasis are also proposed.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81673055 and 81402595).

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Authors and Affiliations

  1. Department of Dermatology, No.1 Hospital of China Medical University, Shenyang, 110001, China

    Xiaolan Zhang, Yajie Yu, Xinghua Gao, Yuanyuan Xu & Long Geng

  2. Department of Dermatology, The first affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China

    Xiaolan Zhang

  3. Liaoning Blood Center, Shenyang, 110001, China

    Jianping Li

  4. Jinzhou City Animal Disease Control and Prevention Center, Jinzhou, 120001, China

    Peng Lian

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  1. Xiaolan Zhang
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  2. Jianping Li
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  3. Yajie Yu
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  5. Xinghua Gao
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  6. Yuanyuan Xu
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  7. Long Geng
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Correspondence to Long Geng.

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All animal experimental procedures were approved and overseen by the Animal Care and Use Committee of the Shenyang Institute of Traditional Chinese Medicine.

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Zhang, X., Li, J., Yu, Y. et al. Shikonin Controls the Differentiation of CD4+CD25+ Regulatory T Cells by Inhibiting AKT/mTOR Pathway. Inflammation 42, 1215–1227 (2019). https://doi.org/10.1007/s10753-019-00982-7

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