Abstract 150: Cytokine Signaling In Intestinal Epithelial Cells As A Regulator Of Microbiota, Inflammation And Atherosclerosis

• DOI: 10.1161/atvb.42.suppl_1.150
• Publication Date: 2022-11-30T18:57:15Z
• Authors: Natalia Kurilenko; Aliia Fatkhullina; Aleksandra Mazitova; Andrew Kossenkov; Sergei Grivennikov; Ekaterina Koltsova
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

While microbiota regulates immunity and was suggested to play a role in atherosclerosis, the specific of cytokine signaling intestinal epithelial cells (IEC) control microbiota, inflammation, vascular disease remains unknown. We previously showed that IL-23 enforces barrier, controls pro-atherogenic bacteria, metabolites, activation myeloid cells, protects from atherosclerosis. Here we investigate IL-23-regulated IL-17 IEC using newly generated Ldlr -/- Il17rc fl/fl VillinCre + mice. found IEC-specific ablation IL-17RC heightened subclinical altered composition, led enhanced atherosclerosis development accompanied by accumulation activated T aortas. Mechanistically, reduced tight junction proteins as well IgA transport lumen due Pigr expression thereby contributing expansion microbiota. RNAseq analysis revealed upregulation multiple inflammatory pathways, including interferon TLR signaling, while several metabolic pathways such fatty acid oxidation pyruvate were downregulated IL17RC mice; implying an important IL-17R microbial metabolism. Our work uncovers novel protective establishes paradigm cytokine-mediated regulation cardiovascular diseases.