Pathogenic microorganisms utilize multiple approaches to break down host immunity in favor of their invasion, of which, cystatin C is one of the soluble factors secreted by parasites reported to affect host immunity in vivo. The cellular targets and mechanisms of action in vivo of cystatin C, however, are far from clear. As professional antigen-presenting cells, dendritic cells (DCs) are first immune cells that contact foreign pathogenic agents or their products to initiate immune responses. We previously reported that cystatin C can regulate the functions of DCs in terms of suppressed CD4+ T cell activation but enhanced Th1/Th17 differentiation via different mechanisms. Here, we further verified these regulatory effects of cystatin C on DCs in vivo. We found that the suppressive role of DC-mediated CD4+ T cell proliferation by cystatin C was partly cell-contact independent and extended to CD8+ T cells in vivo. Although cystatin C-overexpressing DCs trafficked equally as their mock-transduced counterparts, their adoptive transfer suppressed CD8+ T cell immunity and resulted in compromised tumor rejection in both vaccination and treatment regimes. Compared with their role in promoting Th17 differentiation in vivo, cystatin C-transduced DCs had far greater ability to induce T regulatory cells (Tregs), leading to collectively a higher Treg/Th17 ratio in an adoptively transferred disease model, and thus relieved Th17-dependent autoimmunity. Collectively, these data demonstrated strong in vivo evidences for immune regulatory roles of cystatin C in DCs and provided theoretical basis for the application of cystatin C-transduced cell therapy in the treatment or remission of certain autoimmune diseases. (246).

中文翻译：

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胱抑素C抑制树突状细胞功能导致体内免疫力降低。

病原微生物利用多种途径破坏宿主免疫力，以促进其入侵，其中，胱抑素C是据报道寄生虫分泌的可溶因子之一，可在体内影响宿主免疫力。然而，半胱氨酸蛋白酶抑制剂C的细胞靶标和体内作用机制尚不清楚。作为专业的抗原呈递细胞，树突状细胞（DC）是第一个接触外源病原体或其产物以启动免疫反应的免疫细胞。我们以前报道过，胱抑素C可以通过抑制CD4 + T细胞活化来调节DC的功能，但是可以通过不同的机制增强Th1 / Th17的分化。在这里，我们进一步验证了胱抑素C对体内DC的调节作用。我们发现胱抑素C对DC介导的CD4 + T细胞增殖的抑制作用部分独立于细胞接触，并在体内扩展到CD8 + T细胞。尽管过表达胱抑素C的DC的交易量与模拟转导的DC相同，但过继转移抑制了CD8 + T细胞的免疫力，并在疫苗接种和治疗方案中均导致肿瘤排斥反应受损。与它们在体内促进Th17分化的作用相比，胱抑素C转导的DC具有更大的诱导T调节细胞（Tregs）的能力，从而在过继转移的疾病模型中共同提高了Treg / Th17的比率，从而缓解了Th17-依赖性自身免疫。总的来说，这些数据证明了胱抑素C在DC中的免疫调节作用的强有力的体内证据，为胱抑素C转导的细胞疗法在某些自身免疫性疾病的治疗或缓解中的应用提供了理论基础。（246）。