IL-19 Modulates Antiviral Immunity and Inflammation via IL-20RB/STAT3/TRIM22 Signaling Pathway.

Interleukins (ILs) are pleiotropic mediators of immune signaling and represent promising targets for antiviral intervention. Among them, IL-19 is upregulated in response to viral infections, yet its functional significance and mechanistic basis have been poorly defined. This study identifies an unforeseen antiviral activity of IL-19. Mechanistically, we demonstrate that IL-19 signals through the IL-20RB receptor to drive STAT3 phosphorylation, and this activated IL-20RB/STAT3 pathway then induces TRIM22 expression, culminating in enhanced IFN-λ secretion and the direct suppression of viral replication. Importantly, despite significantly curtailing HSV-1 replication in murine brain and lung tissues, IL-19 administration failed to confer a survival benefit, an effect attributable to aggravated pulmonary inflammation. These findings clarify IL-19 as a dual-function cytokine with both protective antiviral and detrimental proinflammatory properties, illustrating the intricate immunomodulatory functions of cytokines during viral infections.