Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.
Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.
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DOI：
10.1038/s41467-022-32849-1
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发表时间：
2022-09-02
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞代谢是免疫细胞功能的基础，但我们对人类树突细胞生物学中代谢影响及其协调免疫反应的能力的了解还很薄弱。在这里，我们使用最近开发的多参数方法绘制了炎症和耐受性单核树突细胞的单细胞代谢状态和免疫特征。单细胞代谢途径激活评分揭示了不同单核树突细胞分化阶段多个代谢途径的同时参与。 GM-CSF/IL4 诱导糖酵解单核细胞快速重编程和线粒体途径瞬时共激活，随后树突状细胞依赖 TLR4 成熟。 mTOR:AMPK 磷酸化平衡的倾斜和 OXPHOS、糖酵解和脂肪酸氧化代谢的上调是代谢亢进和耐受性树突状细胞免疫抑制表型的基础，树突状细胞表现出成熟抗性和以独特的免疫调节受体特征为标志的去分化免疫表型。该单细胞数据集提供了有关影响人类树突状细胞免疫特征的代谢途径的重要见解。评估单个细胞内而不是群体水平的代谢活动具有许多优点。在这里，作者使用基于流式和质量细胞术的方法来评估人类免疫刺激性树突状细胞群和耐受性树突状细胞群之间的代谢差异。
Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages. GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent maturation of dendritic cells. Skewing of the mTOR:AMPK phosphorylation balance and upregulation of OXPHOS, glycolytic and fatty acid oxidation metabolism underpin metabolic hyperactivity and an immunosuppressive phenotype of tolerogenic dendritic cells, which exhibit maturation-resistance and a de-differentiated immune phenotype marked by unique immunoregulatory receptor signatures. This single-cell dataset provides important insights into metabolic pathways impacting the immune profiles of human dendritic cells. Assessing metabolic activity within single cells rather than at a population level has a number of advantages. Here, the authors use a flow and mass cytometry based approach that assess the metabolic differences between populations of human immune stimulatory and tolerogenic dendritic cells.
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影响因子：
2.3
作者：
Ghezzi P
通讯作者：
Ghezzi P
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
20.3
作者：
Everts, Bart;Amiel, Eyal;Pearce, Edward J.
通讯作者：
Pearce, Edward J.
影响因子：
4.1
作者：
Fliesser, Mirjam;Morton, Charles Oliver;Loeffler, Juergen
通讯作者：
Loeffler, Juergen
影响因子：
29
作者：
Artyomov MN;Van den Bossche J
通讯作者：
Van den Bossche J