Down-regulation of microRNA-203-3p initiates type 2 pathology during schistosome infection via elevation of interleukin-33
He, Xing ; Xie, Jun ; Wang, Yange ; Fan, Xiaobin ; Su, Qin ; Sun, Yue ; Lei, Nanhang ; Zhang, Dongmei ; Gao, Guangping ; Pan, Weiqing
Citations
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Subject Area
Files
Embargo Expiration Date
Link to Full Text
Abstract
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.
Source
PLoS Pathog. 2018 Mar 19;14(3):e1006957. doi: 10.1371/journal.ppat.1006957. eCollection 2018 Mar. Link to article on publisher's site