IL ‐35Ig–expressing dendritic cells induce tolerance via Arginase 1

Abstract The cytokine interleukin IL ‐35 is known to exert strong immunosuppressive functions. Indoleamine 2,3‐dioxygenase 1 ( IDO 1) and Arginase 1 (Arg1) are metabolic enzymes that, expressed by dendritic cells ( DC s), contribute to immunoregulation. Here, we explored any possible link between IL ‐35 and the activity of those enzymes. We transfected a single chain IL ‐35Ig gene construct in murine splenic DC s ( DC 35 ) and assessed any IDO 1 and Arg1 activities as resulting from ectopic IL ‐35Ig expression, both in vitro and in vivo. Unlike Ido1 , Arg1 expression was induced in vitro in DC 35 , and it conferred an immunosuppressive phenotype on those cells, as revealed by a delayed‐type hypersensitivity assay. Moreover, the in vivo onset of a tolerogenic phenotype in DC 35 was associated with the detection of CD 25 + CD 39 + , rather than Foxp3 + , regulatory T cells. Therefore, Arg1 , but not Ido1 , expression in DC 35 appears to be an early event in IL ‐35Ig–mediated immunosuppression.