| First Author | Sie C | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 8 | PubMed ID | 35819408 |
| Mgi Jnum | J:328690 | Mgi Id | MGI:7329728 |
| Doi | 10.1084/jem.20212443 | Citation | Sie C, et al. (2022) IL-24 intrinsically regulates Th17 cell pathogenicity in mice. J Exp Med 219(8):e20212443 |
| abstractText | 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. |
