IL-24 intrinsically regulates Th17 cell pathogenicity in mice.

The Journal of experimental medicine 2022 Aug 01

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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 α 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. © 2022 Sie et al.

Citation

Christopher Sie, Ravi Kant, Christian Peter, Andreas Muschaweckh, Monika Pfaller, Lucy Nirschl, Helena Domínguez Moreno, Tereza Chadimová, Gildas Lepennetier, Tanja Kuhlmann, Rupert Öllinger, Thomas Engleitner, Roland Rad, Thomas Korn. IL-24 intrinsically regulates Th17 cell pathogenicity in mice. The Journal of experimental medicine. 2022 Aug 01;219(8)