miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.
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Authors
Perez-Sanchez, Carlos
Barbera Betancourt, Ariana
Lyons, Paul A
Zhang, Zinan
Suo, Chenqu
Lee, James C
McKinney, Eoin F
Modis, Louise K
Ellson, Christian
Smith, Kenneth GC
Publication Date
2022-05-02Journal Title
Journal of Experimental Medicine
ISSN
0022-1007
Publisher
Rockefeller University Press
Volume
219
Issue
5
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
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
Description
Funder: UK National Institute of Health Research Cambridge Biomedical Research Centre
Abstract
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.
Keywords
Monocytes, Humans, Colitis, Inflammatory Bowel Diseases, MicroRNAs, Tumor Necrosis Factor Inhibitors
Sponsorship
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.
Funder references
Medical Research Council (MR/L019027/1)
European Commission Horizon 2020 (H2020) Societal Challenges (733100)
Identifiers
35363256, PMC8980842
External DOI: https://doi.org/10.1084/jem.20211366
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336820
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