Down-regulation of microRNA-203-3p initiates type 2 pathology during schistosome infection via elevation of interleukin-33
UMass Chan AffiliationsDepartment of Microbiology and Physiological Systems
Horae Gene Therapy Center
Immunology of Infectious Disease
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AbstractThe 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.
PLoS Pathog. 2018 Mar 19;14(3):e1006957. doi: 10.1371/journal.ppat.1006957. eCollection 2018 Mar. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40620
RightsCopyright: © 2018 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2018 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.