The Critical Role of AMPKα1 in Regulating Autophagy and Mitochondrial Respiration in IL-15-Stimulated mTORC1Weak Signal-Induced T Cell Memory: An Interplay between Yin (AMPKα1) and Yang (mTORC1) Energy Sensors in T Cell Differentiation

Ara, Anjuman; Wu, Zhaojia; Xu, Aizhang; Ahmed, Khawaja Ashfaque; Leary, Scot C.; Islam, Md. Fahmid; Chibbar, Rajni; Wu, Yue; Xiang, Jim

doi:10.3390/ijms23179534

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…And the enhanced HIF-1α-dependent growth of tumors is associated with increased multifunctionality of CD8 + TILs [112]. In addition, HIF-1α upregulation contributes to the metabolic switch from FAO to glycolysis, thereby promoting effector T cell differentiation [113,114]. For CD4 + T cells, HIF-1α-mediated glycolysis activity and metabolic reprogramming are important for their differentiation and function [115][116][117][118].…”

Section: Challenges and Prospectsmentioning

confidence: 99%

Effects of altered glycolysis levels on CD8+ T cell activation and function

et al. 2023

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CD8+ T cells are an important component of the body’s adaptive immune response. During viral or intracellular bacterial infections, CD8+ T cells are rapidly activated and differentiated to exert their immune function by producing cytokines. Alterations in the glycolysis of CD8+ T cells have an important effect on their activation and function, while glycolysis is important for CD8+ T cell functional failure and recovery. This paper summarizes the importance of CD8+ T cell glycolysis in the immune system. We discuss the link between glycolysis and CD8+ T cell activation, differentiation, and proliferation, and the effect of altered glycolysis on CD8+ T cell function. In addition, potential molecular targets to enhance and restore the immune function of CD8+ T cells by affecting glycolysis and the link between glycolysis and CD8+ T cell senescence are summarized. This review provides new insights into the relationship between glycolysis and CD8+ T cell function, and proposes novel strategies for immunotherapy by targeting glycolysis.

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Section: Challenges and Prospectsmentioning

confidence: 99%

Effects of altered glycolysis levels on CD8+ T cell activation and function

et al. 2023

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“…High levels of IL-15 contribute to the improvement of insulin resistance in postmenopausal women with metabolic syndrome [ 226 ]. IL-15 triggers autophagy in the immune cells, mediating homeostasis and the survival of these cells [ 227 , 228 ]. IL-6 is a pleiotropic cytokine with respect to insulin resistance; while numerous studies have indicated its association with insulin resistance [ 226 – 229 ], others have reported its insulin-sensitizing effects [ 230 , 231 ].…”

Section: Skeletal Muscle Tissuementioning

confidence: 99%

Crosstalk between autophagy and insulin resistance: evidence from different tissues

Sadeghi,

Niknam,

Momeni-Moghaddam

et al. 2023

Eur J Med Res

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Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.

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“…For example, Ara et al . described the effects of the pro-survival cytokine IL-15 on T cells, activating AMPKα1 and upregulating ULK1, ATG7, the mitochondrial fusion protein optic atrophy-1 (OPA1), TFAM, AQP9, CPT1α and Complex I mitochondrial biogenesis protein levels respectively, while also leading to reliance on FAO with concomitant downregulation of hypoxia-inducible factor (HIF)-1α and thus glycolysis [ 73 ]. Interestingly, this mechanism involving γ-chain family cytokines was also shown to be crucial for the complete induction of autophagy in response to TCR and CD28 engagement.…”

Section: Relationship Between Cytokine Release and Autophagy In T Cellsmentioning

confidence: 99%

Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies

Giansanti,

Theinert,

Boeing

et al. 2023

Mol Cancer

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Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.

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The Critical Role of AMPKα1 in Regulating Autophagy and Mitochondrial Respiration in IL-15-Stimulated mTORC1Weak Signal-Induced T Cell Memory: An Interplay between Yin (AMPKα1) and Yang (mTORC1) Energy Sensors in T Cell Differentiation

Cited by 7 publications

References 50 publications

Effects of altered glycolysis levels on CD8+ T cell activation and function

Effects of altered glycolysis levels on CD8+ T cell activation and function

Crosstalk between autophagy and insulin resistance: evidence from different tissues

Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies

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