Control of T Cell Metabolism by Cytokines and Hormones

Abstract

Dynamic, coordinated changes in metabolic pathway activity underpin the protective and inflammatory activity of T cells, through provision of energy and biosynthetic precursors for effector functions, as well as direct effects of metabolic enzymes, intermediates and end-products on signaling pathways and transcriptional mechanisms. Consequently, it has become increasingly clear that the metabolic status of the tissue microenvironment directly influences T cell activity, with changes in nutrient and/or metabolite abundance leading to dysfunctional T cell metabolism and interlinked immune function. Emerging evidence now indicates that additional signals are integrated by T cells to determine their overall metabolic phenotype, including those arising from interaction with cytokines and hormones in their environment. The impact of these on T cell metabolism, the mechanisms involved and the pathological implications are discussed in this review article.

Glutor, a Glucose Transporter Inhibitor, Exerts Antineoplastic Action on Tumor Cells of Thymic Origin: Implication of Modulated Metabolism, Survival, Oxidative Stress, Mitochondrial Membrane Potential, pH Homeostasis, and Chemosensitivity

“…As a result, the low glucose uptake caused by glutor-dependent-inhibition of GLUT would have triggered the observed downregulation in HIF-1a expression. Nevertheless, transcription of GLUT genes is also under the regulation of several HIF-1a independent factors, including the C-myc, K-Ras, PI3K/Akt/mTOR, cytokines, hormones, HOX transcript antisense RNA (HOTAIR), and miRNA (54,(57)(58)(59)(60)(61)(62)(63)(64). Indeed, we also observed glutor-dependent inflection of C-myc.…”

Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients

“…The flux value of each metabolic reaction was predicted by flux sampling, and the flux difference between severe patients and healthy humans was applied to define the regulation state of each reaction. The results showed that extensive elevation of glycolytic fluxes (in HMR_4379, HMR_4373, HMR_4365, HMR_4375, HMR_4363, and HMR_4368) and the serious interception of tricarboxylic acid cycle (in HMR_4139, HMR_8743, and HMR_4652) and electron transport chain (in HMR_6916 and HMR_6918) were basically consistent with aerobic glycolysis of active macrophages and T cells during inflammation [ 12 , 13 ]. Notably, the vigorous purine metabolism mainly containing HMR_4421 was confirmed by one previous metabolomic study of PBMCs in COVID-19 severe patients [ 46 ].…”

“…Importantly, most subpopulations of peripheral blood mononuclear cells (PBMCs) including monocytes, T cells, and B cells, tend to adaptively respond to cytokine levels in the peripheral circulation or local lesions, and these immune metabolic responses are closely related to cell functions [ 12 , 13 , 14 ]. Classically, monocytes or macrophages activated by lipopolysaccharide (LPS) or interferon (IFN) -γ (IFN-γ) are polarized from the M 0 immature phenotype to M 1 pro-inflammatory phenotype, which is characterized by aerobic glycolysis [ 12 ].…”

“…Classically, monocytes or macrophages activated by lipopolysaccharide (LPS) or interferon (IFN) -γ (IFN-γ) are polarized from the M 0 immature phenotype to M 1 pro-inflammatory phenotype, which is characterized by aerobic glycolysis [ 12 ]. The metabolism of activated T cells mainly consists of aerobic glycolysis and a transition from catabolism to anabolism [ 13 ]. The metabolism of T-cell-activated B cells tends to increase the flux of tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) [ 14 ].…”

Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies

“… 131 and Table 4 ). Notably, several biologics influence lipid and lipoprotein metabolism, and it is likely that biologics have additional indirect metabolic actions associated with preventing inflammatory cytokines from binding their receptors, as seen with JAK inhibitors ( 132 , 133 ).…”