Identification of a metabolic-immune crosstalk in Still's disease: monocyte/macrophage-derived immunometabolite itaconate dictates hepatic immunopathology via the CXCL10-CD8 T cell axis - PubMed

4 hours ago

Itaconate, an immunometabolite from monocytes/macrophages, plays a dual role in Still's disease (SD) and macrophage activation syndrome (MAS) by suppressing some pro-inflammatory cytokines (like IL-1β and IL-6) but amplifying CXCL10.
Elevated serum itaconate in SD patients correlates with disease severity, and its production is linked to the ACOD1 enzyme in both human samples and mouse models of MAS.
In a mouse MAS model, deleting the Acod1 gene reduced disease severity, lowered CXCL10 levels, and decreased CD8+ T cell infiltration in the liver, highlighting the CXCL10-CD8 T cell axis in liver immunopathology.
The study suggests caution in using itaconate-based anti-inflammatory therapies for chronic inflammatory diseases due to its paradoxical role in promoting tissue injury through CXCL10 and CD8+ T cells.

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