miR-511-3p, embedded in the macrophage mannose receptor gene, contributes to intestinal inflammation

S. E. M. Heinsbroek, M. L. Squadrito, R. Schilderink, F. W. Hilbers, C. Verseijden, M. Hofmann, A. Helmke, L. Boon, M. E. Wildenberg, J. J. T. H. Roelofs, C. Y. Ponsioen, C. P. Peters, A. A. te Velde, S. Gordon, M. de Palma, W. J. de Jonge

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29 Citations (Scopus)


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
Original languageEnglish
Pages (from-to)960-973
JournalMucosal Immunology
Issue number4
Publication statusPublished - 2016

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