MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling. Issue 1 (7th October 2018)

• Record Type: Journal Article
• Authors: Liu, Xiaomei; Zhou, Feng; Yang, Ying; Wang, Weixiao; Niu, Liping; Zuo, Dongjiao; Li, Xiangyang; Hua, Hui; Zhang, Bo; Kou, Yanbo; Guo, Jingjing; Kong, Fanyun; Pan, Wei; Gao, Dianshuai; Meves, Jessica M.; Sun, Hong; Xue, Min; Zhang, Qingxiu; Wang, Yingwei; Tang, Renxian
• Is Part Of: Glia. Volume 67:Issue 1(2019)
• Page Start: 101
• Page End: 112
• Publication Date: 2018-10-07
• Subjects: astrocytes -- experimental autoimmune encephalomyelitis -- inflammatory cytokines -- microRNA -- multiple sclerosis -- SOCS3; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23530
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Th17 cells and interleukin‐17 (IL‐17) have been found to play an important role in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response to IL‐17, reactive astrocytes accompany with immune cells infiltration and axonal damage in MS/EAE. However, the role and the regulatory mechanism of IL‐17‐activated astrocytes in inflammation and in the EAE process still remain largely unknown. Here, we elucidated that miR‐409‐3p and miR‐1896, as co‐upregulated microRNAs in activated astrocytes and in EAE mice, targeted suppressor of cytokine signaling proteins 3 (SOCS3). Overexpression of miR‐409‐3p or miR‐1896 significantly reduced SOCS3 expression and increased phosphorylation of STAT3 as well as induced the inflammatory cytokines production (IL‐1β, IL‐6, IP‐10, MCP‐1, and KC), CD4 + T cells migration and demyelination, in turn aggravating EAE development. Importantly, the effects of co‐overexpression of miR‐409‐3p and miR‐1896 in vitro or in vivo are strongly co‐operative. In contrast, simultaneously silenced miR‐409‐3p and miR‐1896 co‐operatively ameliorates inflammation and demyelination in the central nervous system of EAE mice. Collectively, our findings highlight that miR‐409‐3p and miR‐1896 co‐ordinately promote the production of inflammatory cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance reactive astrocyte‐directed chemotaxis of CD4 + T cells, leading to aggravate pathogenesis in EAE mice. Co‐inhibition of miR‐409‐3p and miR‐1896 may be a therapeutic target for treating MS and neuroinflammation. Main Points: miR‐409‐3p and miR‐1896, as co‐upregulated microRNAs in activated astrocytes and in EAE mice, cooperatively down‐regulated SOCS3 expression and enhanced inflammatory cytokines production, therefore aggravated inflammation and demyelination in EAE.