High Mitochondrial Respiration and Glycolytic Capacity Represent a Metabolic Phenotype of Human Tolerogenic Dendritic Cells

氧化磷酸化 糖酵解 细胞生物学 生物 树突状细胞 线粒体 新陈代谢 生物化学 化学 免疫系统 免疫学
作者
Frano Malinarich,Kaibo Duan,Raudhah Abdull Hamid,Au Bijin,Wu Xue Lin,Michael Poidinger,Anna‐Marie Fairhurst,John E. Connolly
出处
期刊:Journal of Immunology [American Association of Immunologists]
卷期号:194 (11): 5174-5186 被引量:188
标识
DOI:10.4049/jimmunol.1303316
摘要

Abstract Human dendritic cells (DCs) regulate the balance between immunity and tolerance through selective activation by environmental and pathogen-derived triggers. To characterize the rapid changes that occur during this process, we analyzed the underlying metabolic activity across a spectrum of functional DC activation states, from immunogenic to tolerogenic. We found that in contrast to the pronounced proinflammatory program of mature DCs, tolerogenic DCs displayed a markedly augmented catabolic pathway, related to oxidative phosphorylation, fatty acid metabolism, and glycolysis. Functionally, tolerogenic DCs demonstrated the highest mitochondrial oxidative activity, production of reactive oxygen species, superoxide, and increased spare respiratory capacity. Furthermore, assembled, electron transport chain complexes were significantly more abundant in tolerogenic DCs. At the level of glycolysis, tolerogenic and mature DCs showed similar glycolytic rates, but glycolytic capacity and reserve were more pronounced in tolerogenic DCs. The enhanced glycolytic reserve and respiratory capacity observed in these DCs were reflected in a higher metabolic plasticity to maintain intracellular ATP content. Interestingly, tolerogenic and mature DCs manifested substantially different expression of proteins involved in the fatty acid oxidation (FAO) pathway, and FAO activity was significantly higher in tolerogenic DCs. Inhibition of FAO prevented the function of tolerogenic DCs and partially restored T cell stimulatory capacity, demonstrating their dependence on this pathway. Overall, tolerogenic DCs show metabolic signatures of increased oxidative phosphorylation programing, a shift in redox state, and high plasticity for metabolic adaptation. These observations point to a mechanism for rapid genome-wide reprograming by modulation of underlying cellular metabolism during DC differentiation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
罗颂子发布了新的文献求助10
刚刚
1秒前
一轮明月完成签到 ,获得积分10
2秒前
perdgs发布了新的文献求助10
2秒前
3秒前
3秒前
Siliang完成签到,获得积分10
3秒前
4秒前
4秒前
淬h完成签到,获得积分10
5秒前
聪明的远锋完成签到,获得积分10
5秒前
科研通AI5应助momo采纳,获得10
5秒前
所所应助常尽欢采纳,获得10
7秒前
zfzf0422完成签到 ,获得积分10
8秒前
8秒前
AATRAHASIS完成签到,获得积分10
10秒前
一只小小发布了新的文献求助30
10秒前
沙111完成签到 ,获得积分10
10秒前
淬h发布了新的文献求助10
10秒前
13秒前
13秒前
沙青梦发布了新的文献求助10
15秒前
Lei完成签到,获得积分20
16秒前
16秒前
perdgs完成签到,获得积分10
17秒前
思源应助xiaoxiao采纳,获得10
17秒前
傲娇芷蝶完成签到 ,获得积分10
17秒前
小闵完成签到,获得积分10
18秒前
momo关注了科研通微信公众号
18秒前
bodhi完成签到,获得积分10
19秒前
20秒前
啾啾发布了新的文献求助10
20秒前
FashionBoy应助付创采纳,获得10
21秒前
21秒前
22秒前
简单灵凡发布了新的文献求助10
22秒前
djh发布了新的文献求助10
22秒前
23秒前
常尽欢发布了新的文献求助10
24秒前
25秒前
高分求助中
All the Birds of the World 4000
Production Logging: Theoretical and Interpretive Elements 3000
Les Mantodea de Guyane Insecta, Polyneoptera 2000
Am Rande der Geschichte : mein Leben in China / Ruth Weiss 1500
CENTRAL BOOKS: A BRIEF HISTORY 1939 TO 1999 by Dave Cope 1000
Machine Learning Methods in Geoscience 1000
Resilience of a Nation: A History of the Military in Rwanda 888
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3737713
求助须知:如何正确求助?哪些是违规求助? 3281328
关于积分的说明 10024815
捐赠科研通 2998078
什么是DOI,文献DOI怎么找? 1645034
邀请新用户注册赠送积分活动 782506
科研通“疑难数据库(出版商)”最低求助积分说明 749814