Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages.
Jennifer K Dowling, Remsha Afzal, Linden J Gearing, Mariana P Cervantes-Silva, Stephanie Annett, Gavin M Davis, Chiara De Santi, Nadine Assmann, Katja Dettmer, Daniel J Gough, Glenn R Bantug, Fidinny I Hamid, Frances K Nally, Conor P Duffy, Aoife L Gorman, Alex M Liddicoat, Ed C Lavelle, Christoph Hess, Peter J Oefner, David K Finlay Show all
Nat Commun | Published : 2021
Mitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor ..View full abstract