Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
Publication year
2017Source
Journal of Experimental Medicine, 214, 6, (2017), pp. 1737-1752ISSN
Publication type
Article / Letter to editor

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Organization
Internal Medicine
Journal title
Journal of Experimental Medicine
Volume
vol. 214
Issue
iss. 6
Page start
p. 1737
Page end
p. 1752
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life SciencesAbstract
MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation. miR-223-/y mice presented with exacerbated myeloid-driven experimental colitis with heightened clinical, histopathological, and cytokine readouts. Mechanistically, enhanced NLRP3 inflammasome expression with elevated IL-1beta was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2+ inflammatory monocytes and pharmacologic blockade of IL-1beta or NLRP3 abrogated this phenotype. Generation of a novel mouse line, with deletion of the miR-223 binding site in the NLRP3 3' untranslated region, phenocopied the characteristics of miR-223-/y mice. Finally, nanoparticle-mediated overexpression of miR-223 attenuated experimental colitis, NLRP3 levels, and IL-1beta release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation.
This item appears in the following Collection(s)
- Academic publications [227942]
- Electronic publications [107431]
- Faculty of Medical Sciences [86237]
- Open Access publications [76543]
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