RT Journal Article
T1 miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.
A1 Perez-Sanchez, Carlos
A1 Barbera Betancourt, Ariana
A1 Lyons, Paul A
A1 Zhang, Zinan
A1 Suo, Chenqu
A1 Lee, James C
A1 McKinney, Eoin F
A1 Modis, Louise K
A1 Ellson, Christian
A1 Smith, Kenneth G C
K1 Colitis
K1 Humans
K1 Inflammatory bowel diseases
AB 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.
PB Rockefeller University Press
YR 2022
FD 2022-02-17
LK http://hdl.handle.net/10668/19699
UL http://hdl.handle.net/10668/19699
LA en
NO Perez-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):e20211366
NO 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 BiomedicalResearch Centre.
DS RISalud
RD Apr 18, 2025