T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus

Shan, Juan; Jin, Hua; Xu, Yan

doi:10.3389/fimmu.2020.01027

Cited by 112 publications

(64 citation statements)

References 54 publications

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“…In addition to the effect of cell state, the metabolic characteristics of different subsets of T cells are also different. In the past, it was generally believed that most of the Teffs were metabolized by glycolysis, whereas Tregs were metabolized by oxidative phosphorylation of glucose and fatty acids [16][17][18] . However, in recent years, this dichotomy is thought not accurate.…”

Section: Discussionmentioning

confidence: 99%

Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment

Liu

et al. 2021

Cell Death Dis

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Immunotherapy is expected to become the most promising new treatment for ovarian cancer owing to its immunogenicity. However, immunosuppression in the tumor microenvironment is a major obstacle to the efficacy of tumor therapy. Studies have found different metabolism ways of regulatory T cells (Tregs) in the cancer environment may be related to the immunosuppression and Toll-like receptor 8 (TLR8) can reverse the suppression function of Tregs. But it is still unclear that if the TLR8-mediated function reversal is associated with the change of glucose metabolism of Tregs. It was found that the positive expression rates of Glut1, HIF-1α, and Ki67 in CD4+ Treg cells of OC were significantly higher than that in benign ovarian tumor and HC, and also significantly higher than that in CD4+ Teffs of OC. What’s more, compared with CD4+ Teff group, CD4+ Tregs highly expressed seven genes and three proteins related to glucose metabolism and had higher levels of glucose uptake and glycolysis. After activating TLR8 signal of CD4+ Tregs, the proliferation level of naive CD4+ T cells was higher than that of the control group. At the same time, the expression levels of eight genes and five proteins related to glucose metabolism in CD4+ Treg cells with TLR8 activated were decreased and levels of glucose uptake and glycolysis were also lower. Furthermore, TLR8 signaling also downregulated the mTOR pathway in CD4+ Tregs. CD4+ Tregs pretreated with 2-deoxy-d-Glucose (2-DG) and galloflavin also attenuated the inhibition of Teffs proliferation. Although CD4+ Tregs pretreated with 2-DG and galloflavin before activating TLR8 signal had no significant difference compared with the group only treated with inhibitors, which suggested TLR8-mediated reversal of CD4+ Treg cells inhibitory function in ovarian cancer cells co-cultured microenvironment had a causal relationship with glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment

Liu

et al. 2021

Cell Death Dis

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“…In a number of autoimmune diseases, an altered Th17/Treg ratio has been shown [22], particularly a drastic drop in the T-reg population. In many cases, the successful treatment of a number of systemic autoimmune diseases by using different molecules and treatment approaches may also be linked to the restoration of the Th17/Treg imbalance and/or of cellular functional properties that had been shown for example in MS and SLE [23][24][25][26].…”

Section: Autoimmunitymentioning

confidence: 99%

Relevance of Essential Trace Elements in Nutrition and Drinking Water for Human Health and Autoimmune Disease Risk

et al. 2020

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Trace elements produce double-edged effects on the lives of animals and particularly of humans. On one hand, these elements represent potentially toxic agents; on the other hand, they are essentially needed to support growth and development and confer protection against disease. Certain trace elements and metals are particularly involved in humoral and cellular immune responses, playing the roles of cofactors for essential enzymes and antioxidant molecules. The amount taken up and the accumulation in human tissues decisively control whether the exerted effects are toxic or beneficial. For these reasons, there is an urgent need to re-consider, harmonize and update current legislative regulations regarding the concentrations of trace elements in food and in drinking water. This review aims to provide information on the interrelation of certain trace elements with risk of autoimmune disease, with a particular focus on type 1 diabetes and multiple sclerosis. In addition, an overview of the current regulations and regulatory gaps is provided in order to highlight the importance of this issue for everyday nutrition and human health.

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“…28 Paucity of Tregs leads to Th17/Treg imbalance, which catalyses metabolic aberration in favor of disease progression. 29,30 This might lead to decreased regulation and uncontrolled effector function of the immune system against self-cells. In the present study, the decline in Tregs is possibly not linked to oxidative stress-induced killing as it has a positive correlation with intracellular oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients

Tandon

Anupam

Kaushal

et al. 2020

Lupus

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Systemic Lupus Erythematosus is an autoimmune disease with symptoms pervasive to all organ systems. It affects more females as compared to males (in the ratio 9:1). Oxidative stress plays a major role in the pathogenesis of SLE and other autoimmune diseases. In order to understand the relationship between cell specific oxidative stress and the severity of SLE, this research study involving the estimation of intracellular ROS accumulation in T and NK cell was conducted on SLE patients of North Indian Population. At the same time, to estimate anti-oxidant defense, Keap1 and Nrf2 levels were estimated in these cell types. The relationship between the expression of Killer immunoglobulin receptors i.e., KIR2DL4 & KIR3DL1 and oxidative stress was also evaluated as these receptors are imperative for the function and self-tolerance of NK cells. Oxidative stress was raised along with Keap1 and Nrf2 in T and NK cell subsets in SLE patients. The expression of KIR2DL4 was raised and that of KIR3DL1 was reduced in the NK cells of patients. The intensity of change in expression and its significance varied among the subsets. Nrf2 expression was raised in these species against oxidative stress as the antioxidant defense mechanism pertaining to Keap1-Nrf2 pathway, but the adequacy of response needs to be understood in further studies. The expression of KIR2DL4 and KIR3DL1 varied among the patient and healthy controls and the expression of the latter was found to have a significant positive relationship with plasma Glutathione(reduced) concentration.

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T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus

Cited by 112 publications

References 54 publications

Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment

Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment

Relevance of Essential Trace Elements in Nutrition and Drinking Water for Human Health and Autoimmune Disease Risk

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients

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