Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System,Advanced Science

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Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System
Advanced Science ( IF 14.3 ) Pub Date : 2021-03-01 , DOI: 10.1002/advs.202004979
Jun-Young Park _{1,

2} , Sung Jean Park ₃ , Jun Young Park ₂ , Sang-Hyun Kim ₄ , Song Kwon ₁ , YunJae Jung _{1,

2,

5} , Dongwoo Khang _{1,

2,

6}

Affiliation

The plasma proteins around nanoparticles (NPs) form an outer protein corona, significantly influencing the subsequent immune response. However, it was uncertain whether the protein corona around NPs influences immune response. This study clarified that the immune response mediated by the protein corona is greatly dependent on the type of plasma proteins surrounding the NPs. Structural changes in the unfolded protein corona elevated reactive oxygen species (ROS) levels and induced major proinflammatory cytokine release in both murine and human macrophage cell lines. In contrast, negligible structural changes in the protein corona provoke neither ROS production nor proinflammatory cytokine release. Furthermore, in vivo analysis confirms that a stimulated immune response by an unfolded protein corona triggers selective activation of innate and adaptive immunity in the spleen. Specifically, neutrophils, natural killer cells, and CD8⁺ T cells are overpopulated by unfolded protein corona structures surrounding nanotubes, whereas innate and adaptive immunologic responses are not triggered by a normal protein corona. In conclusion, highly unfolded protein corona structures are strongly correlated with subsequent activation of proinflammatory cytokines and innate immune responses; thus, the protein corona can be used in immune‐enhancing therapy.

中文翻译：

纳米管周围展开的蛋白质电晕影响先天和适应性免疫系统

纳米颗粒（NP）周围的血浆蛋白形成外部蛋白冠，显着影响随后的免疫反应。然而，尚不确定纳米颗粒周围的蛋白冠是否影响免疫反应。这项研究阐明，蛋白冠介导的免疫反应很大程度上取决于纳米颗粒周围的血浆蛋白类型。未折叠蛋白冠的结构变化提高了活性氧（ROS）水平，并诱导小鼠和人类巨噬细胞系中主要促炎细胞因子的释放。相比之下，蛋白质冠中可忽略不计的结构变化既不会引起ROS的产生，也不会引起促炎细胞因子的释放。此外，体内分析证实，未折叠的蛋白冠刺激的免疫反应会选择性激活脾脏中的先天性和适应性免疫。具体来说，中性粒细胞、自然杀伤细胞和 CD8 ⁺ T 细胞被纳米管周围未折叠的蛋白质冠结构所过度填充，而先天性和适应性免疫反应不会由正常的蛋白质冠触发。总之，高度未折叠的蛋白冠结构与随后促炎细胞因子的激活和先天免疫反应密切相关。因此，蛋白冠可用于免疫增强疗法。

更新日期：2021-04-22

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