Arginase is a complex and unique enzyme that plays diverse roles in health and disease. By metabolizing arginine, it can shape the outcome of innate and adaptive immune responses. The immunomodulatory capabilities of arginase could potentially be applied for local immunosuppression or induction of immune tolerance. With the use of an enhanced DNA delivery approach, we designed and studied a DNA-encoded secretable arginase enzyme as a tool for immune modulation and evaluated its immunomodulatory function in vivo. Strong immunosuppression of cluster of differentiation 4 (CD4) and CD8 T cells, as well as macrophages and dendritic cells, was observed in vitro in the presence of an arginase-rich supernatant. To further evaluate the efficacy of DNA-encoded arginase on in vivo immunosuppression against an antigen, a cancer antigen vaccine model was used in the presence or absence of DNA-encoded arginase. Significant in vivo immunosuppression was observed in the presence of DNA-encoded arginase. The efficacy of this DNA-encoded arginase delivery was examined in a local, imiquimod-induced, psoriasis-like, skin-inflammation model. Pretreatment of animals with the synthetic DNA-encoded arginase led to significant decreases in skin acanthosis, proinflammatory cytokines, and costimulatory molecules in extracted macrophages and dendritic cells. These results draw attention to the potential of direct in vivo-delivered arginase to function as an immunomodulatory agent for treatment of local inflammation or autoimmune diseases.

精氨酸酶是一种复杂而独特的酶，在健康和疾病中扮演着多种角色。通过代谢精氨酸，它可以影响先天性和适应性免疫反应的结果。精氨酸酶的免疫调节能力可潜在地用于局部免疫抑制或诱导免疫耐受。通过使用增强的DNA传递方法，我们设计和研究了DNA编码的分泌型精氨酸酶作为免疫调节的工具，并评估了其在体内的免疫调节功能。在富含精氨酸酶的上清液的存在下，体外观察到分化4（CD4）和CD8 T细胞簇以及巨噬细胞和树突状细胞的强免疫抑制作用。为了进一步评估DNA编码精氨酸酶在体内的功效在针对抗原的免疫抑制方面，在存在或不存在DNA编码的精氨酸酶的情况下，使用了癌症抗原疫苗模型。在DNA编码的精氨酸酶存在下，观察到了显着的体内免疫抑制。这种DNA编码的精氨酸酶传递的功效在局部，咪喹莫特诱导，牛皮癣样皮肤炎症模型中进行了检查。用合成的DNA编码的精氨酸酶对动物进行预处理可导致提取的巨噬细胞和树突状细胞中皮肤棘皮症，促炎性细胞因子和共刺激分子的显着降低。这些结果引起人们对直接体内递送精氨酸酶作为治疗局部炎症或自身免疫疾病的免疫调节剂的潜力的关注。