miR-23a contributes to T cellular redox metabolism in juvenile idiopathic oligoarthritis

• Published in: Rheumatology (Oxford, England) England), 2022-05, Vol.61 (6), p.2694-2703
• Main Authors: Rajendiran, Anandhi, Klemm, Patricia, Schippers, Anastasia, Scheufen, Anja, Schwarz, Tobias, Peitz, Joachim, Brandenburg, Lars-Ove, Wagner, Norbert, Consolaro, Alessandro, Raggi, Federica, Bosco, Maria Carla, Luedde, Tom, Foell, Dirk, Denecke, Bernd, Horneff, Gerd, Ohl, Kim, Tenbrock, Klaus
• Format: Article
• Language: English
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keab709

Abstract Objective JIA is a chronic inflammatory disease of unknown origin. The regulation of inflammatory processes involves multiple cellular steps including mRNA transcription and translation. Different miRNAs control these processes tightly. We aimed to determine the roles of specific miRNAs within JIA pathogenesis. Methods We performed a global miRNA expression analysis in parallel in cells from the arthritic joint and peripheral blood of oligoarticular JIA patients and healthy controls. Quantitative RT-PCR analysis was used to verify expression of miRNA in T cells. Ex vivo experiments and flow cytometric analyses were used to analyse proliferation and redox metabolism. Results Global miRNA expression analysis demonstrated a different composition of miRNA expression at the site of inflammation compared with peripheral blood. Bioinformatic analysis of predicted miRNA target genes suggest a huge overrepresentation of genes involved in metabolic and oxidative stress pathways in the inflamed joint. Despite enhanced reactive oxygen species (ROS) levels within the local inflammatory milieu, JIA T cells are hyperproliferative and reveal an overexpression of miR-23a, which is an inhibitor of Peptidyl-prolyl isomerase F (PPIF), the regulator of mitochondrial ROS escape. Mitochondrial ROS escape is diminished in JIA T cells, resulting in their prolonged survival. Conclusion Our data suggest that miRNA-dependent mitochondrial ROS shuttling might be a mechanism that contributes to T cell regulation in JIA at the site of inflammation.