IL-24 intrinsically regulates Th17 cell pathogenicity in mice
2022-08-01 | journal article; research paper
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
IL-24 intrinsically regulates Th17 cell pathogenicity in mice
Sie, C.; Kant, R.; Peter, C.; Muschaweckh, A.; Pfaller, M.; Nirschl, L. & Moreno, H. D. et al. (2022)
Journal of Experimental Medicine, 219(8). DOI: https://doi.org/10.1084/jem.20212443
Documents & Media
Details
- Authors
- 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
- 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 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.
- Issue Date
- 1-August-2022
- Journal
- Journal of Experimental Medicine
- Project
- TRR 274: Checkpoints of Central Nervous System Recovery
TRR 274 | A01: Blimp1 as a checkpoint for distinct functions of CNS Treg cells - Working Group
- RG Korn
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English