Investigation for the mechanisms of immune tolerance against HCV mediated by tryptophan-catalyzing enzyme, IDO

一种色氨酸分解酶，吲哚胺2,3-双加氧酶（IDO），据报道是免疫耐受的诱导剂。我们的目的是澄清IDO是否在慢性丙型肝炎患者（CHC）中被激活及其在免疫应答中的作用。CHC患者血清犬尿氨酸浓度显著高于健康供者，其水平与组织学活动或纤维化评分呈正相关。患者IDO- dc的IDO活性明显高于供者。此外，与来自捐赠者的ido - dc相比，来自患者的ido - dc诱导了更多的调节性T细胞（Tregs）。在IL28B轻微基因型患者中，Peg-IFNα/利巴韦林治疗的SVR患者的Kyn浓度低于非SVR患者。综上所述，CHC患者全身IDO活性增强与肝脏炎症和纤维化程度相关。来自患者的ido - dc容易诱导treg，导致HCV持续存在或对基于干扰素的治疗产生耐药性。

A tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO), is reported to be an inducer of immune tolerance. Our aim was to clarify whether IDO is activated or not in chronic hepatitis C patients (CHC) and its role in immune responses. Serum kynurenine concentration in CHC patients was significantly higher than those in healthy donors, the levels of which were positively correlated with histological activity or fibrosis scores. IDO activity in IDO-DCs from the patients was significantly higher than those from the donors. Furthermore, IDO-DCs from the patients induced more regulatory T cells (Tregs) compared to those from donors. In patients with IL28B minor genotype, Kyn concentration was lower in SVR patients in Peg-IFNα/ribavirin therapy than those in non -SVR patients.In conclusion, systemic IDO activity is enhanced in CHC patients in correlation with the degree of liver inflammation and fibrosis. IDO-DCs from the patients are prone to induce Tregs, resulting in HCV persistence or the resistance to IFN-based therapy.