Genome-wide metabolic model to improve understanding of CD4+ T cell metabolism, immunometabolism and application in drug design

	Genome-wide metabolic model to improve understanding of CD4+ T cell metabolism, immunometabolism and application in drug design
	Han FF 1,2; Li GH 1; Dai SX 1; Huang JF[*]1,3,4
刊名	MOLECULAR BIOSYSTEMS
	2016
卷号	12 期号:2 页码:431-443
通讯作者	huangjf@mail.kiz.ac.cn
合作状况	其它
英文摘要	CD4(+) T cells play a critical role in adaptive immunity and have been well studied in past decades. However, the systematic metabolism features are less clear. Here, we reconstructed the genome-wide metabolic network of naive CD4(+) T cells, CD4T1670, by integrating transcriptome and metabolism data. We performed simulations for three critical metabolic subsystems (carbohydrate metabolism, fatty acid metabolism and glutaminolysis). The results were consistent with most experimental observations. Furthermore, we found that depletion of either glucose or glutamine did not significantly affect ATP production and biomass, but dramatically unbalanced the metabolic network and increased the release of some inflammation or anti-inflammation related factors, such as lysophosphatidylcholine, leukotriene and hyaluronan. Genome-wide single gene knockout analysis showed that acetyl-CoA carboxylase 1 (ACC1) was essential for T cell activation. We further investigated the role of immunometabolic genes in metabolic network stability, and found that over 25% of them were essential. The results also showed that although PTEN is a well-studied proliferation inhibitor, it was essential for maintaining the stability of CD4 metabolic networks. Finally, we applied CD4T1670 to evaluate the side-effects of certain drugs in preclinical experiments. These results suggested that CD4T1670 would be useful in understanding CD4(+) T cells and drug design systematically.
收录类别	SCI
资助信息	This work was supported by the National Basic Research Program of China (Grant No. 2013CB835100), and the National Natural Science Foundation of China (Grant No. 31123005 to J.F.H, No. 31401137 to G.H.L and No. 31401142 to S.X.D.).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9509]
专题	昆明动物研究所_结构生物信息学昆明动物研究所_遗传资源与进化国家重点实验室
作者单位	1.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Eastern Jiaochang Road, Kunming, Yunnan 650223, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, P.R. China 3.KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, P.R. China 4.Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan, Kunming 650223, P.R. China
推荐引用方式 GB/T 7714	Han FF,Li GH,Dai SX,et al. Genome-wide metabolic model to improve understanding of CD4+ T cell metabolism, immunometabolism and application in drug design[J]. MOLECULAR BIOSYSTEMS,2016,12(2):431-443.
APA	Han FF,Li GH,Dai SX,&Huang JF[*].(2016).Genome-wide metabolic model to improve understanding of CD4+ T cell metabolism, immunometabolism and application in drug design.MOLECULAR BIOSYSTEMS,12(2),431-443.
MLA	Han FF,et al."Genome-wide metabolic model to improve understanding of CD4+ T cell metabolism, immunometabolism and application in drug design".MOLECULAR BIOSYSTEMS 12.2(2016):431-443.