Metabolomic and lipidomic signatures associated with activation of human cDC1 (BDCA3+/CD141+) dendritic cells,Immunology

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Metabolomic and lipidomic signatures associated with activation of human cDC1 (BDCA3+/CD141+) dendritic cells
Immunology ( IF 4.9 ) Pub Date : 2021-08-24 , DOI: 10.1111/imm.13409
Farhan Basit ₁ , Tom van Oorschot ₁ , Jessie van Buggenum ₁ , Rico J E Derks ₂ , Sarantos Kostidis ₂ , Martin Giera ₂ , I Jolanda M de Vries _{1,

3}

Affiliation

Dendritic cells (DCs) bridge the connection between innate and adaptive immunity. DCs present antigens to T cells and stimulate potent cytotoxic T-cell responses. Metabolic reprogramming is critical for DC development and activation; however, metabolic adaptations and regulation in DC subsets remains largely uncharacterized. Here, we mapped metabolomic and lipidomic signatures associated with the activation phenotype of human conventional DC type 1, a DC subset specialized in cross-presentation and therefore of major importance for the stimulation of CD8⁺ T cells. Our metabolomics and lipidomic analyses showed that Toll-like receptor (TLR) stimulation altered glycerolipids and amino acids in cDC1. Poly I:C or pRNA stimulation reduced triglycerides and cholesterol esters, as well as various amino acids. Moreover, TLR stimulation reduced expression of glycolysis-regulating genes and did not induce glycolysis. Conversely, cDC1 exhibited increased mitochondrial content and oxidative phosphorylation (OXPHOS) upon TLR3 or TLR7/8 stimulation. Our findings highlight the metabolic adaptations required for cDC1 maturation.

中文翻译：

与人 cDC1 (BDCA3+/CD141+) 树突状细胞活化相关的代谢组学和脂质组学特征

树突状细胞 (DC) 在先天免疫和适应性免疫之间架起了一座桥梁。DC 将抗原呈递给 T 细胞并刺激有效的细胞毒性 T 细胞反应。代谢重编程对于 DC 的发育和激活至关重要；然而，DC 亚群的代谢适应和调节在很大程度上仍未得到表征。在这里，我们绘制了与人类常规 DC 1 型激活表型相关的代谢组学和脂质组学特征，这是一个专门用于交叉呈递的 DC 子集，因此对于刺激 CD8 ^{+具有重要意义}T细胞。我们的代谢组学和脂质组学分析表明，Toll 样受体 (TLR) 刺激改变了 cDC1 中的甘油脂和氨基酸。Poly I:C 或 pRNA 刺激可减少甘油三酯和胆固醇酯以及各种氨基酸。此外，TLR 刺激降低了糖酵解调节基因的表达，并且不诱导糖酵解。相反，cDC1 在 TLR3 或 TLR7/8 刺激下表现出增加的线粒体含量和氧化磷酸化 (OXPHOS)。我们的研究结果强调了 cDC1 成熟所需的代谢适应。

更新日期：2021-08-24

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