Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, People's Republic of China.
J Biosci. 2021;46.
-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL), a small bacterial signaling molecule secreted by , can block dendritic cell (DC) maturation and participate in immune escape, but the underlying mechanism is unclear. We speculate that regulation of DC maturation and function by lncRNAs may be the mechanism by which 3-O-C12-HSL inhibits the immune response. We found that 3-O-C12-HSL increased the expression level of the lncRNA NRIR, impeding monocyte-derived dendritic cell (Mo-DC) maturation. In addition, we observed the effect of NRIR on the expression of CD40, CD80, HLA-DR and IL-6. NRIR overexpression significantly reduced the expression of Mo-DC surface markers, while 3-OC12-HSL did not significantly reduce the expression of Mo-DC surface markers after NRIR knockdown. These results indicate that 3-O-C12-HSL indeed affects the differentiation and maturation of Mo-DCs through NRIR. IL-6 stimulates T cell proliferation and activation, and we found that high NRIR expression reduced IL6 levels. However, under NRIR knockdown, 3-O-C12-HSL did not decrease IL-6 expression, suggesting that 3-O-C12-HSL may affect T cell activation through NRIR. This study is the first to elucidate the important role of a lncRNA in the mechanism of 3-O-C12-HSL activity. It also provides new ideas regarding infection pathogenesis.
3-（辛酰基）-L-高丝氨酸内酯（3-O-C12-HSL）是一种由 分泌的小分子细菌信号分子，可阻断树突状细胞（DC）的成熟并参与免疫逃逸，但具体机制尚不清楚。我们推测，lncRNA 对 DC 成熟和功能的调节可能是 3-O-C12-HSL 抑制免疫反应的机制。我们发现 3-O-C12-HSL 增加了 lncRNA NRIR 的表达水平，从而阻碍单核细胞来源的树突状细胞（Mo-DC）的成熟。此外，我们观察了 NRIR 对 CD40、CD80、HLA-DR 和 IL-6 表达的影响。NRIR 过表达显著降低了 Mo-DC 表面标志物的表达，而在 NRIR 敲低后，3-O-C12-HSL 并未显著降低 Mo-DC 表面标志物的表达。这些结果表明，3-O-C12-HSL 确实通过 NRIR 影响 Mo-DC 的分化和成熟。IL-6 刺激 T 细胞增殖和激活，我们发现高 NRIR 表达降低了 IL-6 水平。然而，在 NRIR 敲低的情况下，3-O-C12-HSL 并未降低 IL-6 的表达，这表明 3-O-C12-HSL 可能通过 NRIR 影响 T 细胞的激活。本研究首次阐明了 lncRNA 在 3-O-C12-HSL 活性机制中的重要作用。它还为 感染发病机制提供了新的思路。
