Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity

Peng, Hao-Yun; Lucavs, Jason; Ballard, Darby J; Das, Jugal Kishore; Kumar, Anil; Wang, Liqing; Ren, Yijie; Xiong, Xiaofang; Song, Jianxun

doi:10.3389/fimmu.2021.652687

Cited by 72 publications

(48 citation statements)

References 100 publications

(204 reference statements)

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“…Glycolysis, glutaminolysis, and fatty acid metabolism are the three main metabolic pathways in CD4+ T cells that function to provide energy. Activated T cells undergo remarkable metabolic changes that are characterized by metabolic reprogramming with increased glycolysis to support cell biosynthesis and function ( 12 ). Metabolic reprogramming is necessary during T-cell activation.…”

Section: Th17 and Treg Cells And The Th17/treg Balancementioning

confidence: 99%

The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

et al. 2021

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Chronic inflammation plays an important role in the development of metabolic diseases. These include obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated fatty liver disease. The proinflammatory environment maintained by the innate immunity, including macrophages and related cytokines, can be influenced by adaptive immunity. The function of T helper 17 (Th17) and regulatory T (Treg) cells in this process has attracted attention. The Th17/Treg balance is regulated by inflammatory cytokines and various metabolic factors, including those associated with cellular energy metabolism. The possible underlying mechanisms include metabolism-related signaling pathways and epigenetic regulation. Several studies conducted on human and animal models have shown marked differences in and the important roles of Th17/Treg in chronic inflammation associated with obesity and metabolic diseases. Moreover, Th17/Treg seems to be a bridge linking the gut microbiota to host metabolic disorders. In this review, we have provided an overview of the alterations in and the functions of the Th17/Treg balance in metabolic diseases and its role in regulating immune response-related glucose and lipid metabolism.

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Section: Th17 and Treg Cells And The Th17/treg Balancementioning

confidence: 99%

The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

et al. 2021

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“…Nevertheless, the model of ROS as "flooding" the cell is still popular in the scientific community, often referred to as "total cellular ROS levels" (Wang et al, 2013(Wang et al, , 2019Dinakar et al, 2016;Kim and Xue, 2020;Loth et al, 2020;Thorne et al, 2021), "intracellular ROS levels" (Tepel et al, 2000;Bensaad et al, 2009;Choi et al, 2011;Lee et al, 2017;Wang et al, 2019Wang et al, , 2021aWei et al, 2019;Zaidieh et al, 2019;Zhang W. et al, 2019;Mendiola et al, 2020;Winitchaikul et al, 2021;Zhong et al, 2021) or simply "ROS levels" (Chen et al, 2012(Chen et al, , 2021Wei et al, 2019;Agarwal and Ganesh, 2020;Kim et al, 2021;Knight et al, 2021;Zeller et al, 2021) in many studies, mainly because of the usage of diffusible ROS probes, which suggest free diffusion of ROS through the cell without regard of the location of ROS production. Mutations, e.g., in cancer cells (Schumacker, 2006;Liou and Storz, 2010;Reczek and Chandel, 2017;Zaidieh et al, 2019;Perillo et al, 2020), pathogenic invasion (West et al, 2011a;Abuaita et al, 2018;Gluschko et al, 2018;Roca et al, 2019) or metabolic disbalance (Li et al, 2016;Mak et al, 2017;Peng et al, 2021) are prominent examples, in which the ...…”

Section: Ros Production: the Dose Makes The Poisonmentioning

confidence: 99%

Reactive Oxygen Species: Not Omnipresent but Important in Many Locations

Herb

Gluschko

Schramm

2021

Front. Cell Dev. Biol.

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Reactive oxygen species (ROS), such as the superoxide anion or hydrogen peroxide, have been established over decades of research as, on the one hand, important and versatile molecules involved in a plethora of homeostatic processes and, on the other hand, as inducers of damage, pathologies and diseases. Which effects ROS induce, strongly depends on the cell type and the source, amount, duration and location of ROS production. Similar to cellular pH and calcium levels, which are both strictly regulated and only altered by the cell when necessary, the redox balance of the cell is also tightly regulated, not only on the level of the whole cell but in every cellular compartment. However, a still widespread view present in the scientific community is that the location of ROS production is of no major importance and that ROS randomly diffuse from their cellular source of production throughout the whole cell and hit their redox-sensitive targets when passing by. Yet, evidence is growing that cells regulate ROS production and therefore their redox balance by strictly controlling ROS source activation as well as localization, amount and duration of ROS production. Hopefully, future studies in the field of redox biology will consider these factors and analyze cellular ROS more specifically in order to revise the view of ROS as freely flowing through the cell.

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“…eEF2K knockdown significantly inhibited monocyte adhesion to human umbilical vein endothelial cells (HUVECs) ( Usui et al, 2013 ). One of the well-characterized inflammatory signals is the cytokine TNF-α, which has been shown to be induced by ROS in endothelial cells and is a significant contributor to inflammation ( Chen et al, 2008 ; Peng et al, 2021 ). Knockdown of eEF2K significantly reduces TNF-α induced ROS production in HUVECs ( Usui et al, 2013 ).…”

Section: Eef2k Activity In Immune Cells and Pathologiesmentioning

confidence: 99%

Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase

Ballard

Peng

Das

et al. 2021

Front. Mol. Biosci.

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Eukaryotic Elongation Factor-2 Kinase (eEF2K) acts as a negative regulator of protein synthesis, translation, and cell growth. As a structurally unique member of the alpha-kinase family, eEF2K is essential to cell survival under stressful conditions, as it contributes to both cell viability and proliferation. Known as the modulator of the global rate of protein translation, eEF2K inhibits eEF2 (eukaryotic Elongation Factor 2) and decreases translation elongation when active. eEF2K is regulated by various mechanisms, including phosphorylation through residues and autophosphorylation. Specifically, this protein kinase is downregulated through the phosphorylation of multiple sites via mTOR signaling and upregulated via the AMPK pathway. eEF2K plays important roles in numerous biological systems, including neurology, cardiology, myology, and immunology. This review provides further insights into the current roles of eEF2K and its potential to be explored as a therapeutic target for drug development.

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Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity

Cited by 72 publications

References 100 publications

The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

Reactive Oxygen Species: Not Omnipresent but Important in Many Locations

Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase

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