Plasmacytoid dendritic cells (pDCs) are specialized producers of Type I interferon (IFN-I) that promote anti-viral and anti-tumor immunity. However, chronic infections and cancer inhibit pDC-derived IFN-I. While the mechanisms of this inhibition are multifarious they can be classified broadly into two categories: i) reduction or ablation of pDC IFN-I-production capacity (functional exhaustion) and/or ii) decrease in pDC numbers (altered population dynamics). Recent work has identified many processes that contribute to suppression of pDC-derived IFN-I during chronic infections and cancer, including sustained stimulation through Toll Like Receptors (TLRs), inhibitory microenvironments, inhibitory receptor ligation, and reduced development from bone marrow progenitors and apoptosis. Emerging success leveraging pDCs in treatment of disease through TLR activation illustrates the therapeutic potential of targeting pDCs. Deeper understanding of the systems that limit pDC-derived IFN-I has the potential to improve these emerging therapies as well as help devising new approaches that harness the outstanding IFN-I-production capacity of pDCs.

中文翻译：

---

感染和癌症抑制 pDC 衍生的 IFN-I。

浆细胞样树突状细胞 (pDC) 是 I 型干扰素 (IFN-I) 的专门生产者，可促进抗病毒和抗肿瘤免疫。然而，慢性感染和癌症会抑制 pDC 衍生的 IFN-I。虽然这种抑制的机制多种多样，但它们可大致分为两类：i) pDC IFN-I 生产能力的减少或消除（功能衰竭）和/或 ii) pDC 数量的减少（改变群体动态）。最近的工作已经确定了许多在慢性感染和癌症期间抑制 pDC 衍生的 IFN-I 的过程，包括通过 Toll 样受体 (TLR) 持续刺激、抑制性微环境、抑制性受体连接以及骨髓祖细胞发育减少和细胞凋亡。通过 TLR 激活利用 pDC 治疗疾病的新成功说明了靶向 pDC 的治疗潜力。更深入地了解限制 pDC 衍生的 IFN-I 的系统有可能改进这些新兴疗法，并有助于设计利用 pDC 出色的 IFN-I 生产能力的新方法。