Down-regulation of microRNA-203-3p initiates type 2 pathology during schistosome infection via elevation of interleukin-33

作者：He, Xing; Xie, Jun; Wang, Yange; Fan, Xiaobin; Su, Qin; Sun, Yue; Lei, Nanhang; Zhang, Dongmei; Gao, Guangping^*; Pan, Weiqing^*

来源：PLoS Pathogens, 2018, 14(3): e1006957.

DOI：10.1371/journal.ppat.1006957

• INNATE LYMPHOID-CELLS
• HEPATIC STELLATE CELLS
• IMMUNE-RESPONSES
• FIBROSIS
• IL-33
• MICE
• INFLAMMATION
• INHIBITION
• JAPONICUM
• PATHWAYS

The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis. We show that miR-203-3p targets interleukin-33 (IL-33), an inducer of type 2 immunity, in hepatic stellate cells to regulate the expansion and IL-13 production of hepatic group 2 innate lymphoid cells during infection. Our study highlights the potential of rAAV8-mediated miR-203-3p elevation as a therapeutic intervention for fibrotic diseases.

• 出版日期2018-3
• 单位中国人民解放军第二军医大学