Human IL-19 regulates immunity through auto-induction of IL-19 and production of IL-10

Abstract

IL-19 is a novel, recently identified member of the IL-10 family of cytokines. We identified IL-10 as a cytokine that was strongly induced in IL-19-stimulated PBMC. IL-19-induced IL-10 secretion was dose-dependent and could be detected in culture supernatants after 3 h of stimulation. Furthermore, quantitative RT-PCR analysis demonstrated that IL-19 stimulation increased the level of IL-10 mRNA present within cells, suggesting that IL-19 is a transcriptional activator of IL-10. IL-19 was also able to induce its own expression, with IL-10 potently down-regulating this IL-19 'auto-induction'. LPS induction of IL-19 expression was also regulated by IL-10, demonstrating that IL-10 is likely an important regulator of human IL-19 induction. Maturation of dendritic cells from human PBMC in the presence of IL-19 resulted in an increase in IL-10 levels within these cells, whereas IL-12 was not affected. These results advance our understanding of the function of this novel cytokine and its regulation within the human immune system, in addition to providing a new insight into the control of the important immunoregulatory cytokine, IL-10.