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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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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. |
format | Online Article Text |
id | pubmed-5460990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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