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Inhibition of CD4 + T cells by fanchinoline via miR506-3p/NFATc1 in Sjögren’s syndrome

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Abstract

The hyperproliferation and hyperactivation of CD4 + T cells in salivary gland tissues are hallmarks of Sjögren’s syndrome (SS). Fangchinoline (Fan) is extracted from the root of Stephania tetrandra Moore, which is used for treating rheumatic diseases in many studies. This study aimed to identify the mechanism underlying the inhibition of CD4 + T cells by Fan in the SS model NOD/ShiLtj mice. In vivo, Fan alleviated the dry mouth and lymphocyte infiltration in the salivary gland tissues of the NOD/ShiLtj mice and inhibited the number of CD4 + T cells in the infiltrating focus. In vitro, Fan’s inhibitory effect on the proliferation of mouse primary CD4 + T cells was verified by CFSE and EdU tests. Furthermore, qRT-PCR and WB analysis confirmed that Fan could inhibit the expression of NFATc1 (Nuclear factor of activated T-cells, cytoplasmic 1) by upregulating miR-506-3p. Dual luciferase reporter gene assay suggested that miR-506-3p interacted with NFATc1. CFSE and EdU tests showed that Fan could inhibit the proliferation of CD4 + T cells through miR-506-3p/NFATc1. The key role of NFATc1 in the activation of CD4 + T cells and the high expression of NFATc1 in samples from SS patients suggested that NFATc1 might become a therapeutic target for SS. In vivo, 11R-VIVIT (NFATc1 inhibitor) alleviated SS-like symptoms. This study not only explained the new mechanism of Fan inhibiting proliferation of CD4 + T cells and alleviating SS-like symptoms but also provided NFATc1 as a potential target for the subsequent research and treatment of SS.

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Data available on request from the authors.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81771089), and the Biological sample bank project of Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (YBKB201907).

Funding

National Natural Science Foundation of China, 81771089, Chuangqi Yu, Biological sample bank project of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, YBKB201907, Chuangqi Yu

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Author notes

  1. Yanxiong Shao and Jiayao Fu contributed equally to this work.

Authors and Affiliations

  1. Department of Oral Surgery, Shanghai Ninth People’s HospitalCollege of Stomatology, National Center for Stomatology, National Clinical Research Center of Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Zhizaoju Road 639, Shanghai, 200011, China

    Yanxiong Shao, Jiayao Fu, Tianle Zhan, Junhao Yin, Jiabao Xu, Yifan Lu, Qi Luo & Chuangqi Yu

  2. Department of Stomatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China

    Yanxiong Shao

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  1. Yanxiong Shao
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  2. Jiayao Fu
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Contributions

YXS and CQY designed the study; YXS, JYF, TLZ, JHY, YFL, QL performed the experiments and collected and analyzed the data; YXS, JYF and CQY wrote and revised the manuscript. YXS and JYF contributed equally to this work.

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Correspondence to Chuangqi Yu.

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Shao, Y., Fu, J., Zhan, T. et al. Inhibition of CD4 + T cells by fanchinoline via miR506-3p/NFATc1 in Sjögren’s syndrome. Inflammopharmacol 31, 2431–2443 (2023). https://doi.org/10.1007/s10787-023-01279-w

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