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代谢微环境塑造树突状细胞功能。

Shaping of Dendritic Cell Function by the Metabolic Micro-Environment.

机构信息

Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.

出版信息

Front Endocrinol (Lausanne). 2020 Aug 28;11:555. doi: 10.3389/fendo.2020.00555. eCollection 2020.


DOI:10.3389/fendo.2020.00555
PMID:33013685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7493661/
Abstract

Nutrients are required for growth and survival of all cells, but are also crucially involved in cell fate determination of many cell types, including immune cells. There is a growing appreciation that the metabolic micro-environment also plays a major role in shaping the functional properties of dendritic cells (DCs). Under pathological conditions nutrient availability can range from a very restricted supply, such as seen in a tumor micro-environment, to an overabundance of nutrients found in for example obese adipose tissue. In this review we will discuss what is currently known about the metabolic requirements for DC differentiation and immunogenicity and compare that to how function and fate of DCs under pathological conditions can be affected by alterations in environmental levels of carbohydrates, lipids and amino acids as well as by other metabolic cues, including availability of oxygen, redox homeostasis and lactate levels. Many of these insights have been generated using model systems, which have revealed highly diverse effects of different metabolic cues on DC function. However, they also stress the importance of shifting toward more physiologically relevant experimental settings to be able to fully delineate the role of the metabolic surroundings in its full complexity in shaping the functional properties of DCs in health and disease.

摘要

营养素是所有细胞生长和存活所必需的,但对于许多细胞类型(包括免疫细胞)的细胞命运决定也至关重要。人们越来越认识到,代谢微环境在塑造树突状细胞(DC)的功能特性方面也起着主要作用。在病理条件下,营养物质的可利用性范围从非常有限的供应(如肿瘤微环境中所见)到例如肥胖脂肪组织中发现的大量营养物质。在这篇综述中,我们将讨论目前已知的 DC 分化和免疫原性的代谢需求,并将其与病理条件下 DC 功能和命运如何受到环境中碳水化合物、脂质和氨基酸水平以及其他代谢线索(包括氧的可用性、氧化还原平衡和乳酸水平)的改变的影响进行比较。许多这些见解是使用模型系统产生的,这些系统揭示了不同代谢线索对 DC 功能的高度多样化影响。然而,它们也强调了转向更生理相关的实验设置的重要性,以便能够全面描述代谢环境在塑造健康和疾病中 DC 功能特性的复杂性方面的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fa2/7493661/bcead21429fc/fendo-11-00555-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fa2/7493661/bcead21429fc/fendo-11-00555-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fa2/7493661/bcead21429fc/fendo-11-00555-g0001.jpg

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本文引用的文献

[1]
The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8 T-cell Responses and Promotes Tumor Growth.

Cancer Immunol Res. 2020-8

[2]
The lactate receptor GPR81 promotes breast cancer growth via a paracrine mechanism involving antigen-presenting cells in the tumor microenvironment.

Oncogene. 2020-2-19

[3]
CD73 Blockade Promotes Dendritic Cell Infiltration of Irradiated Tumors and Tumor Rejection.

Cancer Immunol Res. 2020-2-11

[4]
Human Plasma-like Medium Improves T Lymphocyte Activation.

iScience. 2020-1-24

[5]
Reprogramming of fatty acid metabolism in cancer.

Br J Cancer. 2019-12-10

[6]
New aspects of amino acid metabolism in cancer.

Br J Cancer. 2019-12-10

[7]
Adenosine Receptor Signaling Targets Both PKA and Epac Pathways to Polarize Dendritic Cells to a Suppressive Phenotype.

J Immunol. 2019-11-13

[8]
Oxidative Stress Enhances Dendritic Cell Responses to .

Immunohorizons. 2019-11-5

[9]
Dendritic Cells Require PINK1-Mediated Phosphorylation of BCKDE1α to Promote Fatty Acid Oxidation for Immune Function.

Front Immunol. 2019-10-15

[10]
Metabolic regulation of gene expression by histone lactylation.

Nature. 2019-10-23

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