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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

37 Scopus citations

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.

Original languageEnglish
Pages (from-to)960-973
Number of pages14
JournalMucosal Immunology
Volume9
Issue number4
DOIs
StatePublished - 01 07 2016
Externally publishedYes

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