Metabolism in Invariant Natural Killer T Cells: An Overview

Yarosz, Emily L; Chang, Cheong Hee; Kumar, Ajay

doi:10.20900/immunometab20210010

Cited by 9 publications

(9 citation statements)

References 54 publications

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“…Invariant natural killer T (iNKT) cells, the main category of natural killer T cells and a subpopulation of mature innate T lymphocytes [ 51 ], were identified as essential players in immunometabolism due to their capacity to respond to self-derived or microbially derived lipid antigens, such us α-galactosylceramide (α-GalCer), which is presented by CD1 molecules on APCs. Similar to these APCs, iNKT cells act as a link between the innate and the adaptive immune system, and they are able to produce the highest amounts of Th1, Th2, Th17, or regulatory cytokines upon activation [ 51 , 52 , 53 , 54 ]. Moreover, there is evidence of communication between cellular metabolic and immune signaling pathways for proper iNKT cell development and function.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, there is evidence of communication between cellular metabolic and immune signaling pathways for proper iNKT cell development and function. Thus, functionally, these cells present an anti-inflammatory or prohomeostatic role in disease development or inflammatory activity, with relevant roles in host defense [ 54 ].…”

Section: Resultsmentioning

confidence: 99%

“…In this sense, it has been reported that inhibition of the mTOR pathway with rapamycin can balance the response between regulatory and effector T cells [ 72 ]. Moreover, it was proposed that Treg cells perform FAO for energy and survival, similar to memory CD4 + T cells [ 54 ].…”

Section: Resultsmentioning

confidence: 99%

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Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

et al. 2023

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Nutraceuticals act as cellular and functional modulators, contributing to the homeostasis of physiological processes. In an inflammatory microenvironment, these functional foods can interact with the immune system by modulating or balancing the exacerbated proinflammatory response. In this process, immune cells, such as antigen-presenting cells (APCs), identify danger signals and, after interacting with T lymphocytes, induce a specific effector response. Moreover, this conditions their change of state with phenotypical and functional modifications from the resting state to the activated and effector state, supposing an increase in their energy requirements that affect their intracellular metabolism, with each immune cell showing a unique metabolic signature. Thus, nutraceuticals, such as polyphenols, vitamins, fatty acids, and sulforaphane, represent an active option to use therapeutically for health or the prevention of different pathologies, including obesity, metabolic syndrome, and diabetes. To regulate the inflammation associated with these pathologies, intervention in metabolic pathways through the modulation of metabolic energy with nutraceuticals is an attractive strategy that allows inducing important changes in cellular properties. Thus, we provide an overview of the link between metabolism, immune function, and nutraceuticals in chronic inflammatory processes associated with obesity and diabetes, paying particular attention to nutritional effects on APC and T cell immunometabolism, as well as the mechanisms required in the change in energetic pathways involved after their activation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

et al. 2023

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“…The development of invariant natural killer T (iNKT) cells is more sensitive to changes in mitochondrial electron transport chain function than conventional αβT cells ( 149 ). There have been several informative reviews recently, so we won’t go over those details here ( 150 – 152 ).…”

Section: Thymocytes Return To a Resting State From The Small Dp Stage...mentioning

confidence: 99%

Metabolic regulation of T cell development

Zhang

Lin²,

Zhang³

et al. 2022

Front. Immunol.

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T cell development in the thymus is tightly controlled by complex regulatory mechanisms at multiple checkpoints. Currently, many studies have focused on the transcriptional and posttranslational control of the intrathymic journey of T-cell precursors. However, over the last few years, compelling evidence has highlighted cell metabolism as a critical regulator in this process. Different thymocyte subsets are directed by distinct metabolic pathways and signaling networks to match the specific functional requirements of the stage. Here, we epitomize these metabolic alterations during the development of a T cell and review several recent works that provide insights into equilibrating metabolic quiescence and activation programs. Ultimately, understanding the interplay between cellular metabolism and T cell developmental programs may offer an opportunity to selectively regulate T cell subset functions and to provide potential novel therapeutic approaches to modulate autoimmunity.

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“…In particular, the metabolic balance between glycolysis and oxidative phosphorylation (OXPHOS) shapes the differentiation and functions of CD4 + Th cells, Foxp3 + regulatory T cells (Tregs), cytotoxic CD8 + T cells, and macrophages 18 . The development and functions of i NKT cells may also depend on their metabolism: while the evidence to date is quite limited 19 , the thymic development of i NKT cells and their inflammatory cytokine production as mature cells associate with changes in their glycolysis:OXPHOS balance 20 . Moreover, peripheral i NKT-cell functions are regulated by their levels of reactive oxygen species, which are byproducts of aerobic metabolism 21 .…”

Section: Introductionmentioning

confidence: 99%

De novofatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness

Koh

Woo

Yoo

et al. 2023

Preprint

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Invariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in iNKT cells is very limited. It is also not clear whether such metabolic regulation of iNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediatedde novofatty-acid synthesis is required for the survival of iNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lung iNKT cells from WT mice that were developing asthma. Cd4-CreAcc1fl/fl mice failed to develop OVA-induced and HDM-induced asthma. Moreover, iNKT cell-deficient mice that were reconstituted with ACC1-deficient iNKT cells failed to develop asthma, unlike when WT iNKT cells were transferred. ACC1 deficiency in iNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR)γ, but increased glycolytic capacity that promoted iNKT-cell death. Furthermore, circulating iNKT cells from allergic-asthma patients expressed higher ACC1 and PPARγ levels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus,de novofatty-acid synthesis prevents iNKT-cell death via an ACC1-FABP-PPARγ axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.

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Metabolism in Invariant Natural Killer T Cells: An Overview

Cited by 9 publications

References 54 publications

Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism

Metabolic regulation of T cell development

De novofatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness

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