IL-24 intrinsically regulates Th17 cell pathogenicity in mice

Area of Science:

• Immunology
• Cellular Biology
• Mitochondrial Function

Background:

• T helper 17 (Th17) cells can drive severe immunopathology.
• Mechanisms restricting pathogenic Th17 cell functions are less understood compared to other T cell types.

Purpose of the Study:

• To elucidate cell-intrinsic mechanisms that control Th17 cell pathogenicity.
• To identify the role of Interleukin-24 (IL-24) in regulating Th17 responses.

Main Methods:

• Investigated the interaction of IL-24 with mitochondrial components.
• Examined the role of NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 13 (Grim19) in Th17 cells.
• Assessed STAT3 localization and function within mitochondria and the nucleus.
• Utilized experimental autoimmune encephalomyelitis models.

Main Results:

• Th17 cells produce IL-24, which induces IL-10 secretion.
• IL-24 localizes to the inner mitochondrial membrane and interacts with Grim19.
• This interaction promotes STAT3 accumulation in the mitochondrial compartment.
• Mitochondrial STAT3 acts as a rheostat, limiting nuclear STAT3 signaling and Th17 pathogenicity.

Conclusions:

• IL-24-mediated mitochondrial STAT3 accumulation is a novel cell-intrinsic mechanism to restrict Th17 pathogenicity.
• This pathway contributes to IL-10 production and limits immunopathology in experimental autoimmune encephalomyelitis.