Cellular metabolism dictates T cell effector function in health and disease

Kolan, Shrikant S.; Li, Gaoyang; Wik, Jonas Aakre; Malachin, Giulia; Guo, Shuai; Kolan, Pratibha; Skålhegg, Bjørn Steen

doi:10.1111/sji.12956

Cited by 14 publications

(11 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is reported that important transcription factors and cytokines, as well as MEKi and other inhibitors in the process of T cell differentiation, induce the generation of T SCM by regulating T cell-related metabolic enzymes (77-79) (Figure 3). Signals from TCR, costimulatory molecules, and growth factors lead to the activation of signaling pathways that promote transcriptional programs that are critical to effector function (80)(81)(82). In memory T cells, cellular stress, such as growth factor deprivation or a low ratio of ATP/AMP, will activate AMP-activated protein kinase (AMPK) and inhibit mTOR signaling (83).…”

Section: Oxidative Metabolic Pathway Of T Scm Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapeutic Potential of T Memory Stem Cells

Yang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Memory T cells include T memory stem cells (TSCM) and central memory T cells (TCM). Compared with effector memory T cells (TEM) and effector T cells (TEFF), they have better durability and anti-tumor immunity. Recent studies have shown that although TSCM has excellent self-renewal ability and versatility, if it is often exposed to antigens and inflammatory signals, TSCM will behave as a variety of inhibitory receptors such as PD-1, TIM-3 and LAG-3 expression, and metabolic changes from oxidative phosphorylation to glycolysis. These changes can lead to the exhaustion of T cells. Cumulative evidence in animal experiments shows that it is the least differentiated cell in the memory T lymphocyte system and is a central participant in many physiological and pathological processes in humans. It has a good clinical application prospect, so it is more and more important to study the factors affecting the formation of TSCM. This article summarizes and prospects the phenotypic and functional characteristics of TSCM, the regulation mechanism of formation, and its application in treatment of clinical diseases.

show abstract

Section: Oxidative Metabolic Pathway Of T Scm Cellsmentioning

confidence: 99%

“…These studies indicate that the regulation of glycolysis and metabolism is the key factor in inducing the formation of T SCM . Therefore, targeted metabolic checkpoints can make T cells differentiate into memory and provide more young T cells for immunotherapy (74,81,82,86).…”

Section: Oxidative Metabolic Pathway Of T Scm Cellsmentioning

confidence: 99%

Immunotherapeutic Potential of T Memory Stem Cells

Yang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…We have briefly summarized some knowledge on T-cell metabolism in situation of infections by virus and bacteria. Research over the last couple of decades have revealed that T-cell metabolism is closely linked, not only to proliferation and clonal expansion, but that cell-specific metabolism also dictate cell differentiation programs and reflect effector functions ( 136 ). As detailed here, T-cell metabolism may in addition aid pathogen clearance or confer resistance to infections by virus and bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Exhausted T cells also display a distinct metabolic phenotype, with reduced glucose uptake as well as mitochondrial dysfunction, which reduces capacity for oxidative metabolism. The presence of extracellular metabolites as well as low abundance of important nutrients may further inhibit metabolism and prevent the appropriate T cell activity ( 135 , 136 ).…”

Section: T Cell Metabolism: From Quiescence To Effector Functionmentioning

confidence: 99%

T Cell Metabolism in Infection

Wik

Skålhegg

2022

Front. Immunol.

View full text Add to dashboard Cite

T lymphocytes (T cells) are divided into two functionally different subgroups the CD4+ T helper cells (Th) and the CD8+ cytotoxic T lymphocytes (CTL). Adequate CD4 and CD8 T cell activation to proliferation, clonal expansion and effector function is crucial for efficient clearance of infection by pathogens. Failure to do so may lead to T cell exhaustion. Upon activation by antigen presenting cells, T cells undergo metabolic reprograming that support effector functions. In this review we will discuss how metabolic reprograming dictates functionality during viral infections using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) as examples. Moreover, we will briefly discuss T cell metabolic programs during bacterial infections exemplified by Mycobacterium tuberculosis (MT) infection.

show abstract

“…Obesity, aging, and associated co-morbidities commonly lead to metabolic reprogramming of human cells [1]. It becomes more and more evident that metabolism tightly controls T cell effector function [2]. Therefore, targeting metabolic pathways of T cells is a promising therapeutic intervention [3].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Palmowski

Gebhardt

Reichel

et al. 2021

Immuno

View full text Add to dashboard Cite

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.

show abstract

Cellular metabolism dictates T cell effector function in health and disease

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 132 publications

Immunotherapeutic Potential of T Memory Stem Cells

Immunotherapeutic Potential of T Memory Stem Cells

T Cell Metabolism in Infection

The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Contact Info

Product

Resources

About