Department of Experimental Medicine, University of Perugia, Perugia, Italy.
J Cell Mol Med. 2019 May;23(5):3757-3761. doi: 10.1111/jcmm.14215. Epub 2019 Feb 22.
The cytokine interleukin IL-35 is known to exert strong immunosuppressive functions. Indoleamine 2,3-dioxygenase 1 (IDO1) and Arginase 1 (Arg1) are metabolic enzymes that, expressed by dendritic cells (DCs), 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 DCs (DC ) and assessed any IDO1 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 , 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 was associated with the detection of CD25 CD39 , rather than Foxp3 , regulatory T cells. Therefore, Arg1, but not Ido1, expression in DC appears to be an early event in IL-35Ig-mediated immunosuppression.
细胞因子白细胞介素 IL-35 已知具有很强的免疫抑制功能。吲哚胺 2,3-双加氧酶 1（IDO1）和精氨酸酶 1（Arg1）是代谢酶，由树突状细胞（DC）表达，有助于免疫调节。在这里，我们探讨了 IL-35 与这些酶活性之间的任何可能联系。我们在鼠脾 DC（DC）中转染了单链 IL-35Ig 基因构建体，并评估了由于异位 IL-35Ig 表达而导致的 IDO1 和 Arg1 活性，无论是在体外还是体内。与 Ido1 不同，Arg1 在体外的 DC 中被诱导表达，并赋予这些细胞免疫抑制表型，如迟发型超敏反应试验所揭示的那样。此外，在 DC 中耐受表型的体内出现与 CD25 CD39、而不是 Foxp3 调节性 T 细胞的检测相关。因此，Arg1 的表达，而不是 Ido1，在 IL-35Ig 介导的免疫抑制中似乎是一个早期事件。
