miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.
Barbera Betancourt, Ariana
Lyons, Paul A
Lee, James C
McKinney, Eoin F
Modis, Louise K
Smith, Kenneth GC
Journal of Experimental Medicine
Rockefeller University Press
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Perez-Sanchez, C., Barbera Betancourt, A., Lyons, P. A., Zhang, Z., Suo, C., Lee, J. C., McKinney, E. F., et al. (2022). miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.. Journal of Experimental Medicine, 219 (5) https://doi.org/10.1084/jem.20211366
Funder: UK National Institute of Health Research Cambridge Biomedical Research Centre
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.
Monocytes, Humans, Colitis, Inflammatory Bowel Diseases, MicroRNAs, Tumor Necrosis Factor Inhibitors
This study was funded via the GSK/Cambridge Strategic Alliance Varsity Funding Program, Wellcome (project grant 094227/Z/10/Z and Investigator Award 200871/Z/16/Z), the European Union H2020 project SYSCID (grant 733100), the UK Medical Research Council (program grant MR/L019027), and the UK National Institute of Health Research Cambridge Biomedical Research Centre.
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/1810/336820
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/