2. Academic Validation
  3. Inhibition of CD4 + T cells by fanchinoline via miR506-3p/NFATc1 in Sjögren's syndrome

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

  • Inflammopharmacology. 2023 Jul 14. doi: 10.1007/s10787-023-01279-w.
Yanxiong Shao # 1 2,  Jiayao Fu # 1,  Tianle Zhan 1,  Junhao Yin 1,  Jiabao Xu 1,  Yifan Lu 1,  Qi Luo 1,  Chuangqi Yu 3
Affiliations

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.
  • 2 Department of Stomatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
  • 3 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. [email protected].
  • # Contributed equally.
PMID: 37450074 DOI: 10.1007/s10787-023-01279-w
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.

Keywords

CD4 + T cell; Fangchinoline; NFATc1; Sjögren’s syndrome; miR-506-3p.

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