Perez-Sanchez, CarlosBarbera Betancourt, ArianaLyons, Paul AZhang, ZinanSuo, ChenquLee, James CMcKinney, Eoin FModis, Louise KEllson, ChristianSmith, Kenneth G C2023-05-032023-05-032022-02-17Perez-Sanchez C, Barbera Betancourt A, Lyons PA, Zhang Z, Suo C, Lee JC, et al. miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease. J Exp Med. 2022 May 2;219(5):e20211366http://hdl.handle.net/10668/19699MicroRNAs are critical regulators of gene expression controlling cellular processes including inflammation. We explored their role in the pathogenesis of inflammatory bowel disease (IBD) and identified reduced expression of miR-374a-5p in IBD monocytes that correlated with a module of up-regulated genes related to the inflammatory response. Key proinflammatory module genes, including for example TNFα, IL1A, IL6, and OSM, were inversely correlated with miR-374a-5p and were validated in vitro. In colonic biopsies, miR-374a-5p was again reduced in expression and inversely correlated with the same inflammatory module, and its levels predicted subsequent response to anti-TNF therapy. Increased miR-374a-5p expression was shown to control macrophage-driven inflammation by suppressing proinflammatory mediators and to reduce the capacity of monocytes to migrate and activate T cells. Our findings suggest that miR-374a-5p reduction is a central driver of inflammation in IBD, and its therapeutic supplementation could reduce monocyte-driven inflammation in IBD or other immune-mediated diseases.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ColitisHumansInflammatory bowel diseasesMicroRNAsMonocytesTumor necrosis factor inhibitorsresearch article35363256open accessInhibidores del factor de necrosis tumoralMicroARNsMonocitos10.1084/jem.202113661540-9538PMC8980842https://rupress.org/jem/article-pdf/219/5/e20211366/1430697/jem_20211366.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980842/pdf