title: miR-511-3p, embedded in the macrophage mannose receptor gene, contributes to intestinal inflammation.
abstract: MiR-511-3p is embedded in intron 5 of the CD206/MRC1 gene Mrc1, expressed by macrophage and dendritic cell populations. CD206 and miR-511-3p expression are co-regulated, and their contribution to intestinal inflammation is unclear. We investigated their roles in intestinal inflammation in both mouse and human systems. Colons of CD206-deficient mice displayed normal numbers of monocytes, macrophage, and dendritic cells. In experimental colitis, CD206-deficient mice had attenuated inflammation compared with wild-type (WT) mice. However, neither a CD206 antagonist nor a blocking antibody reproduced this phenotype, suggesting that CD206 was not involved in this response. Macrophages isolated from CD206-deficient mice had reduced levels of miR-511-3p and Tlr4 compared with WT, which was associated with reduced pro-inflammatory cytokine production upon lipopolysaccharides (LPS) and fecal supernatant stimulation. Macrophages overexpressing miR-511-3p showed 50% increase of Tlr4 mRNA, whereas knockdown of miR-511-3p reduced Tlr4 mRNA levels by 60%, compared with scrambled microRNA (miRNA)-transduced cells. Response to anti-tumor necrosis factor (TNF) treatment has been associated with elevated macrophage CD206 expression in the mucosa. However, in colon biopsies no statistically significant change in miR-511-3p was detected. Taken together, our data show that miR-511-3p controls macrophage-mediated microbial responses and is involved in the regulation of intestinal inflammation.
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: S E M
authors.initials: SE
authors.lastname: Heinsbroek
authors.affiliation: The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: M L
authors.initials: ML
authors.lastname: Squadrito
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Schilderink
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: F W
authors.initials: FW
authors.lastname: Hilbers
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Verseijden
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hofmann
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Helmke
authors.affiliation: EPIRUS Biopharmaceuticals Netherlands BV, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Boon
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Wildenberg
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: J J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: C Y
authors.initials: CY
authors.lastname: Ponsioen
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: C P
authors.initials: CP
authors.lastname: Peters
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: Te Velde
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Gordon
authors.affiliation: The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: De Palma
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: de Jonge
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D016264:Dextran Sulfate; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C578471:MIRN511 microRNA, human; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D035683:MicroRNAs; C578472:Mirn511 microRNA, mouse; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016264:Dextran Sulfate