BACKGROUND Control of the inflammatory response is critical to maintaining homeostasis, and failure to do so contributes to the burden of chronic inflammation associated with several disease states. The mechanisms that underlie immunosuppression, however, remain largely unknown. Although defects in autophagy machinery have been associated with inflammatory pathologic conditions, we now appreciate that autophagic components participate in noncanonical pathways distinct from classical autophagy. We have previously demonstrated that LC3-associated phagocytosis (LAP), a noncanonical autophagic process dependent on Rubicon (rubicon autophagy regulator [RUBCN]), contributes to immunosuppression. OBJECTIVE We used Rubcn-/- mice to examine the role of the LAP pathway in mediating the UV-induced immunotolerant program in a model of contact hypersensitivity (CHS). METHODS Flow cytometry and transcriptional analysis were used to measure immune cell infiltration and activation in the skin of Rubcn+/+ and Rubcn-/- mice during the CHS response. RESULTS Here, we demonstrate that LAP is required for UV-induced immunosuppression and that UV exposure induces a broadly anti-inflammatory transcriptional program dependent on Rubicon. Rubcn-/- mice are resistant to UV-induced immunosuppression and instead display exaggerated inflammation in a model of CHS. Specifically, RUBCN deficiency in CD301b+ dermal dendritic cells results in their increased antigen presentation capacity and subsequent hyperactivation of the CD8+ T-cell response. CONCLUSIONS LAP functions to limit the immune response and is critical in maintaining the balance between homeostasis and inflammation.

中文翻译：

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真皮树突状细胞中的非经典自噬介导紫外线照射的免疫抑制作用。

背景控制炎症反应对于维持体内平衡至关重要，如果不这样做会加重与几种疾病状态相关的慢性炎症的负担。然而，免疫抑制的机制仍然很大程度上未知。尽管自噬机制的缺陷与炎症病理状况有关，但我们现在认识到自噬成分参与了不同于经典自噬的非经典途径。我们之前已经证明 LC3 相关吞噬作用 (LAP) 是一种依赖于 Rubicon（rubicon 自噬调节剂 [RUBCN]）的非经典自噬过程，有助于免疫抑制。目的 我们使用 Rubcn-/- 小鼠来检查 LAP 通路在介导接触性超敏反应 (CHS) 模型中紫外线诱导的免疫耐受程序中的作用。方法流式细胞术和转录分析用于测量Rubcn+/+和Rubcn-/-小鼠在CHS反应过程中皮肤的免疫细胞浸润和活化。结果 在这里，我们证明 LAP 是紫外线诱导的免疫抑制所必需的，并且紫外线暴露诱导依赖于 Rubicon 的广泛抗炎转录程序。Rubcn-/- 小鼠对紫外线诱导的免疫抑制具有抵抗力，而是在 CHS 模型中表现出过度的炎症。具体而言，CD301b+ 真皮树突状细胞中的 RUBCN 缺乏会导致其抗原呈递能力增加和随后的 CD8+ T 细胞反应过度激活。