Details

Autor(en) / Beteiligte

• Sie, Christopher
• Kant, Ravi
• Peter, Christian
• Muschaweckh, Andreas
• Pfaller, Monika
• Nirschl, Lucy
• Moreno, Helena Domínguez
• Chadimová, Tereza
• Lepennetier, Gildas
• Kuhlmann, Tanja
• Öllinger, Rupert
• Engleitner, Thomas
• Rad, Roland
• Korn, Thomas

Titel

IL-24 intrinsically regulates Th17 cell pathogenicity in mice

Ist Teil von

• The Journal of experimental medicine, 2022-08, Vol.219 (8)

Ort / Verlag

Rockefeller University Press

Erscheinungsjahr

2022

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.