%0 Journal Article
%T Down-regulation of microRNA-203-3p initiates type 2 pathology during schistosome infection via elevation of interleukin-33
%A Dongmei Zhang
%A Guangping Gao
%A Jun Xie
%A Nanhang Lei
%A Qin Su
%A Weiqing Pan
%A Xiaobin Fan
%A Xing He
%A Yange Wang
%A Yue Sun
%J PLOS Pathogens: A Peer-Reviewed Open-Access Journal
%D 2018
%R https://doi.org/10.1371/journal.ppat.1006957
%X 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.
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006957