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

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.