Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and functions of monocyte-derived dendritic cells (DC), lowering their capacity to stimulate T cell proliferation, development of Th1 and Th17 cells, and T-cell mediated cytotoxicity. Additionally, GQD-treated DC potentiated Th2 polarization, and induced suppressive CD4⁺CD25^highFoxp3⁺ regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowered the ROS generation and nuclear translocation of NF-κB in DC. The activity of mammalian target of rapamycin (mTOR) was reduced by GQD, which correlated with the increase in transcription of autophagy genes and autophagic flux in DC. Genetic suppression of autophagy impaired the pro-tolerogenic effects of GQD on DC. Our results suggest that GQD-triggered autophagy promotes tolerogenic functions in monocyte-derived DC, which could be beneficial in inflammatory T-cell mediated pathologies, but also harmful in GQD-based anti-cancer therapy.

中文翻译：

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石墨烯量子点通过自噬依赖性致耐受性树突状细胞的诱导抑制促炎性T细胞反应

石墨烯量子点（GQD）是原子级的纳米级碳薄板，具有出色的理化和生物学特性，使其在治疗学中的应用具有吸引力。然而，对其免疫调节特性的研究不足，特别是在人原代免疫细胞中。我们发现无毒剂量的GQD抑制了人类外周血单核细胞促炎和T辅助（Th）1细胞因子的产生，并增加了抗炎和Th2细胞因子的产生。虽然无法直接影响T细胞，但GQD损害了单核细胞衍生的树突状细胞（DC）的分化和功能，降低了它们刺激T细胞增殖，Th1和Th17细胞发育以及T细胞介导的细胞毒性的能力。此外，经GQD处理的DC增强了Th2极化，⁺ CD25^高Foxp3 ⁺调节性T细胞。在以不依赖于动力的，依赖胆固醇的方式内化后，GQD降低了DC中ROS的生成和NF-κB的核易位。GQD降低了哺乳动物雷帕霉素靶标（mTOR）的活性，这与DC中自噬基因的转录和自噬通量的增加有关。自噬的遗传抑制削弱了GQD对DC的促致癌作用。我们的结果表明，GQD触发的自噬促进单核细胞来源的DC的致耐受功能，这可能对炎症性T细胞介导的病理学有益，但对基于GQD的抗癌治疗也有害。