IL-24 intrinsically regulates Th17 cell pathogenicity in mice

Sie, Christopher; Kant, Ravi; Peter, Christian; Muschaweckh, Andreas; Pfaller, Monika; Nirschl, Lucy; Moreno, Helena Dominguez; Chadimova, Tereza; Lepennetier, Gildas; Kuhlmann, Tanja; Ollinger, Rupert; Engleitner, Thomas; Rad, Roland und Korn, Thomas (2022): IL-24 intrinsically regulates Th17 cell pathogenicity in mice. In: Journal of Experimental Medicine, Bd. 219, Nr. 8, e20212443

Abstract

In certain instances, Th17 responses are associated with severe immunopathology. T cell-intrinsic mechanisms that restrict pathogenic effector functions have been described for type 1 and 2 responses but are less well studied for Th17 cells. Here, we report a cell-intrinsic feedback mechanism that controls the pathogenicity of Th17 cells. Th17 cells produce IL-24, which prompts them to secrete IL-10. The IL-10-inducing function of IL-24 is independent of the cell surface receptor of IL-24 on Th17 cells. Rather, IL-24 is recruited to the inner mitochondrial membrane, where it interacts with the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 13 (also known as Grim19), a constituent of complex I of the respiratory chain. Together, Grim19 and IL-24 promote the accumulation of STAT3 in the mitochondrial compartment. We propose that IL-24-guided mitochondrial STAT3 constitutes a rheostat to blunt extensive STAT3 deflections in the nucleus, which might then contribute to a robust IL-10 response in Th17 cells and a restriction of immunopathology in experimental autoimmune encephalomyelitis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198