Dendritic cells (DCs) are critical for bridging innate and adaptive immunity. They do so by presenting antigens to T cells, and by expressing diverse molecules that further promote T cell activation, differentiation and memory formation. During this process, intracellular and extracellular factors can perturb the protein-folding capacity of endoplasmic reticulum (ER) and induce a cellular state of "ER stress," which is controlled and resolved by the unfolded protein response (UPR). Interestingly, various studies have shown that DCs can activate UPR-related pathways even in the absence of global ER stress, and that this process can modulate their normal activity. In other settings, such as cancer, adverse microenvironmental conditions have been demonstrated to evoke severe ER stress and persistent activation of the UPR in tumor-infiltrating DCs. This process disrupts their metabolism and local antigen-presenting capacity, hence impeding the initiation and maintenance of anti-cancer immunity. Here, we review recent findings on how canonical and non-canonical UPR activation impacts DC immunobiology at the steady-state, upon activation via pattern recognition receptors, and under diverse pathological conditions. We also discuss the potential therapeutic implications that targeting the UPR in DCs may have in the context of cancer and in other pathologies such as graft-versus-host disease.

中文翻译：

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内质网应激反应对树突状细胞免疫生物学的影响。

树突状细胞（DC）对于桥接先天和适应性免疫至关重要。它们通过向T细胞呈递抗原，并表达进一步促进T细胞活化，分化和记忆形成的各种分子来实现。在此过程中，细胞内和细胞外因子可能干扰内质网（ER）的蛋白质折叠能力，并诱导“ ER应激”的细胞状态，该状态由未折叠的蛋白质反应（UPR）控制和解决。有趣的是，各种研究表明，即使在没有全局ER压力的情况下，DC也可以激活与UPR相关的途径，并且该过程可以调节其正常活动。在其他情况下，例如癌症，已经证明不利的微环境条件会引起严重的内质网应激，并在肿瘤浸润性DC中引起UPR的持续活化。该过程破坏了它们的代谢和局部抗原呈递能力，从而阻碍了抗癌免疫力的启动和维持。在这里，我们回顾了最近的发现，关于经典和非经典的UPR激活如何在稳态，通过模式识别受体激活以及在各种病理情况下影响DC免疫生物学。我们还讨论了在癌症和其他病理情况（例如移植物抗宿主病）中针对DCs的UPR可能具有的潜在治疗意义。在这里，我们回顾了最近的发现，关于经典和非经典的UPR激活如何在稳态，通过模式识别受体激活以及在各种病理情况下影响DC免疫生物学。我们还讨论了在癌症和其他病理情况（例如移植物抗宿主病）中针对DCs的UPR可能具有的潜在治疗意义。在这里，我们回顾了最近的发现，关于经典和非经典的UPR激活如何在稳态，通过模式识别受体激活以及在各种病理情况下影响DC免疫生物学。我们还讨论了在癌症和其他病理情况（例如移植物抗宿主病）中针对DCs的UPR可能具有的潜在治疗意义。