Ivermectin Protects Against Experimental Autoimmune Encephalomyelitis in Mice by Modulating the Th17/Treg Balance Involved in the IL-2/STAT5 Pathway

被引:12
|
作者
Xie, Yu [1 ,2 ,3 ]
Jin, Chaolei [1 ,2 ]
Sang, Hongzhen [1 ,2 ]
Liu, Wenhua [1 ,2 ]
Wang, Junpeng [1 ,2 ]
机构
[1] Henan Univ, Huaihe Hosp, Infect & Immun Inst, 115 Ximen St, Kaifeng 475000, Peoples R China
[2] Henan Univ, Huaihe Hosp, Translat Med Ctr, 115 Ximen St, Kaifeng 475000, Peoples R China
[3] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China
基金
中国国家自然科学基金;
关键词
ivermectin; T cells; autoimmune diseases; multiple sclerosis; CD4(+) T cell subsets; CELL; RECEPTORS; ROLES; IL-2; MECHANISMS;
D O I
10.1007/s10753-023-01829-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
-Multiple sclerosis (MS), a T-cell-mediated autoimmune disease that affects the central nervous system (CNS), is characterized by white matter demyelination, axon destruction, and oligodendrocyte degeneration. Ivermectin, an anti-parasitic drug, has anti-inflammatory, anti-tumor, and antiviral properties. However, to date, there are no in-depth studies on the effect of ivermectin on the function effector of T cells in murine experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we conducted in vitro experiments and found that ivermectin inhibited the proliferation of total T cells (CD3(+)) and their subsets (CD4(+) and CD8(+) T cells) as well as T cells secreting the pro-inflammatory cytokines IFN-gamma and IL-17A; ivermectin also increased IL-2 production and IL-2R alpha (CD25) expression, which was accompanied by an increase in the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg). Importantly, ivermectin administration reduced the clinical symptoms of EAE mice by preventing the infiltration of inflammatory cells into the CNS. Additional mechanisms showed that ivermectin promoted Treg cells while inhibiting pro-inflammatory Th1 and Th17 cells and their IFN-gamma and IL-17 secretion; ivermectin also upregulated IL-2 production from MOG(35-55)-stimulated peripheral lymphocytes. Finally, ivermectin decreased IFN-gamma and IL-17A production and increased IL-2 level, CD25 expression, and STAT5 phosphorylation in the CNS. These results reveal a previously unknown etiopathophysiological mechanism by which ivermectin attenuates the pathogenesis of EAE, indicating that it may be a promising option for T-cell-mediated autoimmune diseases such as MS.
引用
收藏
页码:1626 / 1638
页数:13
相关论文
共 50 条
  • [41] Effects of Bu Shen Yi Sui Capsule on Th17/Treg cytokines in C57BL/6 mice with experimental autoimmune encephalomyelitis
    Zheng, Qi
    Yang, Tao
    Fang, Ling
    Liu, Lei
    Liu, Haolong
    Zhao, Hui
    Zhao, Yiyi
    Guo, Hongzhu
    Fan, Yongping
    Wang, Lei
    BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2015, 15
  • [42] Effects of Bu Shen Yi Sui Capsule on Th17/Treg cytokines in C57BL/6 mice with experimental autoimmune encephalomyelitis
    Qi Zheng
    Tao Yang
    Ling Fang
    Lei Liu
    Haolong Liu
    Hui Zhao
    Yiyi Zhao
    Hongzhu Guo
    Yongping Fan
    Lei Wang
    BMC Complementary and Alternative Medicine, 15
  • [43] Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis
    Mao, Qi-Fen
    Shang-Guan, Zui-Fei
    Chen, Hong-Lei
    Huang, Kai
    ANNALS OF TRANSLATIONAL MEDICINE, 2019, 7 (16)
  • [44] JAK2/STAT3 Pathway Inhibition by AG490 Ameliorates Experimental Autoimmune Encephalomyelitis via Regulation of Th17 Cells and Autophagy
    Xue, Yumei
    Zhang, Lu
    Chu, Lifang
    Song, Zhe
    Zhang, Bing
    Su, Xiaohui
    Liu, Wanhu
    Li, Xiaobing
    NEUROSCIENCE, 2024, 552 : 65 - 75
  • [45] Recombinant adiponectin alleviates abortion in mice by regulating Th17/Treg imbalance via p38MAPK-STAT5 pathway
    Li, Weihong
    Geng, Lihong
    Liu, Xiru
    Gui, Wenwu
    Qi, Hongbo
    BIOLOGY OF REPRODUCTION, 2019, 100 (04) : 1008 - 1017
  • [46] IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors
    Lyu, Shuyan
    Fang, Zhengyu
    Hu, Yiping
    Zhang, Miaomiao
    He, Jiaxin
    Wang, Xiaocheng
    He, Juan
    Gao, Xu
    Wang, Hongli
    Xu, Damo
    Wang, Qingwen
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (23)
  • [47] Activation of the Notch signaling pathway disturbs the CD4+/CD8+, Th17/Treg balance in rats with experimental autoimmune uveitis
    Yin, Xuewei
    Liu, Bin
    Wei, Huixia
    Wu, Shanshan
    Guo, Lijie
    Xu, Furu
    Liu, TingTing
    Bi, Hongsheng
    Guo, Dadong
    INFLAMMATION RESEARCH, 2019, 68 (09) : 761 - 774
  • [48] Activation of the Notch signaling pathway disturbs the CD4+/CD8+, Th17/Treg balance in rats with experimental autoimmune uveitis
    Xuewei Yin
    Bin Liu
    Huixia Wei
    Shanshan Wu
    Lijie Guo
    Furu Xu
    TingTing Liu
    Hongsheng Bi
    Dadong Guo
    Inflammation Research, 2019, 68 : 761 - 774
  • [49] Regulation of the Th17/Treg balance by human umbilical cord mesenchymal stem cell-derived exosomes protects against acute experimental colitis
    Heidari, Neda
    Abbasi-Kenarsari, Hajar
    Namaki, Saeed
    Baghaei, Kaveh
    Zali, Mohammad Reza
    Mirsanei, Zahra
    Hashemi, Seyed Mahmoud
    EXPERIMENTAL CELL RESEARCH, 2022, 419 (01)
  • [50] Treatment of IL-21R-Fc control autoimmune arthritis via suppression of STAT3 signal pathway mediated regulation of the Th17/Treg balance and plasma B cells
    Ryu, Jun-Geol
    Lee, Jennifer
    Kim, Eun-Kyung
    Seo, Hyeon-beom
    Park, Jin-Sil
    Lee, Seon-Yeong
    Moon, Young-Mee
    Yoo, Seok-Ho
    Park, Young-woo
    Park, Sung-Hwan
    Cho, Mi-La
    Kim, Ho-Youn
    IMMUNOLOGY LETTERS, 2015, 163 (02) : 143 - 150