Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome

Neudecker, V; Haneklaus, M; Jensen, O; Khailova, L; Masterson, JC; Tye, H; Biette, K; Jedlicka, P; Brodsky, KS; Gerich, ME; Mack, M; Robertson, AAB; Cooper, MA; Furuta, GT; Dinarello, CA; O&#39;Neill, LA; Eltzschig, HK; Masters, SL; McNamee, EN

Author(s): Neudecker, V; Haneklaus, M; Jensen, O; Khailova, L; Masterson, JC; Tye, H; Biette, K; Jedlicka, P; Brodsky, KS; Gerich, ME; Mack, M; Robertson, AAB; Cooper, MA; Furuta, GT; Dinarello, CA; O'Neill, LA; Eltzschig, HK; Masters, SL; McNamee, EN;
Details: Publication Year 2017-05-09,Volume 214,Issue #6,Page 1737-1752
Journal Title: Journal of Experimental Medicine
Publication Type: Journal Article
Abstract: 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.
Publisher: Rockefeler Uni Press
Research Division(s): Inflammation
PubMed ID: 28487310
Publisher's Version: https://doi.org/10.1084/jem.20160462
Open Access at Publisher's Site: https://doi.org/10.1084/jem.20160462
NHMRC Grants: NHMRC/1057815, NHMRC/1099262,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-05-30 09:30:49

Last Modified: 2018-07-09 03:39:24