Many tumors display alterations in the biosynthetic pathways of glycosylation, resulting in increased expression of specific tumor-associated glycan structures. Expression of these altered glycan structures is associated with metastasis and poor prognosis. Antigen presenting cells can recognize tumor-associated glycan structures, including the truncated O-glycan Tn antigen, via specific glycan receptors. Tn antigen-mediated activation of the C-type lectin MGL on dendritic cells induces regulatory T cells via the enhanced secretion of IL-10. Although these findings indicate that MGL engagement by glycan ligands can modulate immune responses, the impact of MGL ligation on dendritic cells is still not completely understood. Therefore, we employed RNA sequencing, GO term enrichment and pathway analysis on human monocyte-derived dendritic cells stimulated with two different MGL glycan ligands. Our analyses revealed a reduced expression of genes coding for key enzymes involved in the glycolysis pathway, TCA cycle, and oxidative phosphorylation. In concordance with this, extracellular flux analysis confirmed the decrease in glycolytic activity upon MGL triggering in human dendritic cells. To our knowledge, we are the first to report a diminished glycolytic activity of human dendritic cells upon C-type lectin stimulation. Overall, our findings highlight the impact of tumor-associated glycans on dendritic cell biology and metabolism and will increase our understanding on how glycans can shape immunity.

许多肿瘤在糖基化的生物合成途径中显示出改变，从而导致特定的肿瘤相关聚糖结构的表达增加。这些改变的聚糖结构的表达与转移和不良预后有关。抗原呈递细胞可以识别与肿瘤相关的聚糖结构，包括截短的Ø-聚糖Tn抗原，通过特定的聚糖受体。Tn抗原介导的树突状细胞上C型凝集素MGL的激活通过增强的IL-10分泌诱导调节性T细胞。尽管这些发现表明聚糖配体与MGL的结合可以调节免疫反应，但MGL连接对树突状细胞的影响仍未完全了解。因此，我们对两种不同的MGL聚糖配体刺激的人单核细胞来源的树突状细胞进行了RNA测序，GO术语富集和途径分析。我们的分析表明，糖酵解途径，TCA循环和氧化磷酸化所涉及的关键酶的编码基因的表达降低。与此相一致，细胞外通量分析证实了人树突状细胞中MGL触发后糖酵解活性降低。据我们所知，我们是第一个报道在C型凝集素刺激下人树突状细胞的糖酵解活性减弱的研究。总体而言，我们的发现突出了肿瘤相关聚糖对树突状细胞生物学和新陈代谢的影响，并将加深我们对聚糖如何影响免疫力的理解。