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

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 inflammasom...

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Autores principales: Neudecker, Viola, Haneklaus, Moritz, Jensen, Owen, Khailova, Ludmila, Masterson, Joanne C., Tye, Hazel, Biette, Kathryn, Jedlicka, Paul, Brodsky, Kelley S., Gerich, Mark E., Mack, Matthias, Robertson, Avril A.B., Cooper, Matthew A., Furuta, Glenn T., Dinarello, Charles A., O’Neill, Luke A., Eltzschig, Holger K., Masters, Seth L., McNamee, Eóin N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460990/
https://www.ncbi.nlm.nih.gov/pubmed/28487310
http://dx.doi.org/10.1084/jem.20160462
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author Neudecker, Viola
Haneklaus, Moritz
Jensen, Owen
Khailova, Ludmila
Masterson, Joanne C.
Tye, Hazel
Biette, Kathryn
Jedlicka, Paul
Brodsky, Kelley S.
Gerich, Mark E.
Mack, Matthias
Robertson, Avril A.B.
Cooper, Matthew A.
Furuta, Glenn T.
Dinarello, Charles A.
O’Neill, Luke A.
Eltzschig, Holger K.
Masters, Seth L.
McNamee, Eóin N.
author_facet Neudecker, Viola
Haneklaus, Moritz
Jensen, Owen
Khailova, Ludmila
Masterson, Joanne C.
Tye, Hazel
Biette, Kathryn
Jedlicka, Paul
Brodsky, Kelley S.
Gerich, Mark E.
Mack, Matthias
Robertson, Avril A.B.
Cooper, Matthew A.
Furuta, Glenn T.
Dinarello, Charles A.
O’Neill, Luke A.
Eltzschig, Holger K.
Masters, Seth L.
McNamee, Eóin N.
author_sort Neudecker, Viola
collection PubMed
description 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-1β was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2(+) inflammatory monocytes and pharmacologic blockade of IL-1β 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-1β release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation.
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spelling pubmed-54609902017-12-05 Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome Neudecker, Viola Haneklaus, Moritz Jensen, Owen Khailova, Ludmila Masterson, Joanne C. Tye, Hazel Biette, Kathryn Jedlicka, Paul Brodsky, Kelley S. Gerich, Mark E. Mack, Matthias Robertson, Avril A.B. Cooper, Matthew A. Furuta, Glenn T. Dinarello, Charles A. O’Neill, Luke A. Eltzschig, Holger K. Masters, Seth L. McNamee, Eóin N. J Exp Med Research Articles 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-1β was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2(+) inflammatory monocytes and pharmacologic blockade of IL-1β 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-1β release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation. The Rockefeller University Press 2017-06-05 /pmc/articles/PMC5460990/ /pubmed/28487310 http://dx.doi.org/10.1084/jem.20160462 Text en © 2017 Neudecker et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Neudecker, Viola
Haneklaus, Moritz
Jensen, Owen
Khailova, Ludmila
Masterson, Joanne C.
Tye, Hazel
Biette, Kathryn
Jedlicka, Paul
Brodsky, Kelley S.
Gerich, Mark E.
Mack, Matthias
Robertson, Avril A.B.
Cooper, Matthew A.
Furuta, Glenn T.
Dinarello, Charles A.
O’Neill, Luke A.
Eltzschig, Holger K.
Masters, Seth L.
McNamee, Eóin N.
Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
title Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
title_full Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
title_fullStr Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
title_full_unstemmed Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
title_short Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome
title_sort myeloid-derived mir-223 regulates intestinal inflammation via repression of the nlrp3 inflammasome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460990/
https://www.ncbi.nlm.nih.gov/pubmed/28487310
http://dx.doi.org/10.1084/jem.20160462
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