%0 Journal Article
%A Perez-Sanchez, Carlos
%A Barbera Betancourt, Ariana
%A Lyons, Paul A
%A Zhang, Zinan
%A Suo, Chenqu
%A Lee, James C
%A McKinney, Eoin F
%A Modis, Louise K
%A Ellson, Christian
%A Smith, Kenneth G C
%T miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.
%D 2022
%U http://hdl.handle.net/10668/19699
%X 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.
%K Colitis
%K Humans
%K Inflammatory bowel diseases
%~