Interleukin-19 ameliorates drug-induced liver injury by limiting proinflammatory macrophage infiltration via SUMOylation of C/EBPβ.

Recombinant IL-19 significantly suppresses proinflammatory macrophage infiltration and attenuates acetaminophen-induced liver injury in mice, linked to reduced S100A8/A9+ macrophage accumulation.

• Why it matters: The inflammatory mechanisms driving acetaminophen-induced liver injury remain poorly understood, limiting therapeutic options for acute liver failure.
• What they did: Il19-deficient and myeloid cell-specific Il20r2 knockout mice were challenged with acetaminophen, with hepatic macrophage subsets profiled by single-cell RNA sequencing. IL-19 was tested for effects on infiltration, and macrophage C/EBPβ was examined for SUMOylation-dependent control of proinflammatory gene expression.
• The result: IL-19 promotes post-translational SUMOylation of C/EBPβ, downregulating C/EBPβ-dependent proinflammatory genes including those regulating S100A8/A9, thereby ameliorating early-stage injury.

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