miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.
J Exp Med
Rockefeller University Press
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Perez-Sanchez, C., Barbera Betancourt, A., Lyons, P., Zhang, Z., Suo, C., Lee, J. C., McKinney, E., et al. (2022). miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.. J Exp Med, 219 (5), e20211366. https://doi.org/10.1084/jem.20211366
MicroRNAs 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.
Colitis, Humans, Inflammatory Bowel Diseases, MicroRNAs, Monocytes, Tumor Necrosis Factor Inhibitors
Medical Research Council (MR/L019027/1)
European Commission Horizon 2020 (H2020) Societal Challenges (733100)
External DOI: https://doi.org/10.1084/jem.20211366
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336809
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/