Metabolic regulation of pathogenic autoimmunity: therapeutic targeting

Teng, Xiangyu; Cornaby, Caleb; Li, Wei; Morel, Laurence

doi:10.1016/j.coi.2019.07.001

Cited by 29 publications

(26 citation statements)

References 46 publications

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“…The combination of 2DG with metformin, which inhibits complex I of the mt electron transport chain (ETC), reduced the number of these pathogenic T cells and reversed lupus pathogenesis in mice . These results indicate that targeting glycolysis, either alone or in combination with other drugs such as metformin, presents a therapeutic potential for lupus . 2DG has been used in clinical trials in oncology without successful outcomes and with some safety concerns .…”

Section: Glycolysis and Lupusmentioning

confidence: 99%

“…23 These results indicate that targeting glycolysis, either alone or in combination with other drugs such as metformin, presents a therapeutic potential for lupus. 12 2DG has been used in clinical trials in oncology without successful outcomes and with some safety concerns. 185 Other glycolytic enzymes have been targeted in mouse models in which inflammatory and/or autoreactive T cells play a role.…”

Section: G Lycolys Is and Lupusmentioning

confidence: 99%

“…This includes small clinical trials in which lupus patients have seen a reduction in disease activity following treatment with metabolic inhibitors. 11,12 Here, we review how the major metabolic pathways control the activation and differentiation of the immune cell types that are involved in lupus, as well as the studies that have been directly conducted in lupus preclinical models or in lupus patients. These studies are summarized in Table 1 along with the treatments with metabolic inhibitors that have been successful in preclinical models of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…Recent publications have reviewed how immunometabolism controls rheumatic diseases, including systemic lupus erythematosus (SLE), which is, with rheumatoid arthritis, the autoimmune disease with the most advanced understanding of cellular metabolism. This includes small clinical trials in which lupus patients have seen a reduction in disease activity following treatment with metabolic inhibitors . Here, we review how the major metabolic pathways control the activation and differentiation of the immune cell types that are involved in lupus, as well as the studies that have been directly conducted in lupus preclinical models or in lupus patients.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic determinants of lupus pathogenesis

Teng

Brown

Choi

et al. 2020

Immunological Reviews

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The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4 + T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues. K E Y W O R D Sglucose, glutamine, lupus, metabolic inhibitors, metabolism

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Section: Glycolysis and Lupusmentioning

confidence: 99%

Section: G Lycolys Is and Lupusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic determinants of lupus pathogenesis

Teng

Brown

Choi

et al. 2020

Immunological Reviews

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“…This prompted an examination of known or potential metabolic features of the GC response induced by pathogens or autoantigens. In addition, the different metabolic demands reported between autoreactive T FH cells and pathogen-specific T FH cells 8 open a new window of opportunity to selectively target autoreactive cells and to dissect the mechanisms that distinguish the differentiation of pathogen-and autoantigen-induced T FH cells 9 . We also review what is known about the metabolic regulation of follicular regulatory T (T FR ) cells, a specialized subset of regulatory T (Treg) cells that exert immunosuppressive functions in GC 10 .…”

Section: Introductionmentioning

confidence: 99%

Immune metabolism regulation of the germinal center response

Choi

Morel

2020

Exp Mol Med

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The humoral immune response requires germinal centers to produce high-affinity antigen-specific antibodies that counter pathogens. Numerous studies have provided a better understanding of how metabolic pathways regulate the development, activation and functions of immune cells. Germinal centers are transient, highly dynamic microanatomic structures that develop in lymphoid organs during a T-cell-dependent humoral immune response. Analysis of germinal centers provides an opportunity to understand how metabolic programs control the differentiation and function of highly specialized germinal center B cells and follicular helper CD4 + T cells. Targeting immunometabolism during the germinal center response may afford the possibility to improve vaccine design and to develop new therapies to alleviate autoimmunity. In this review, we discuss the major metabolic pathways that are used by germinal center B and T cells, as well as the plasma cells that they produce, all of which are influenced by the microenvironment of this unique structure of the adaptive immune system.

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Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T‐ and B‐cell interactions

Barberis,

Rojas López

2024

Clinical & Translational Med

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The interplay between the immune system and the metabolic state of a cell is intricate. In all phases of an immune response, the corresponding metabolic changes shall occur to support its modulation, in addition to the signalling through the cytokine environment and immune receptor stimulation. While autoimmune disorders may develop because of a metabolic imbalance that modulates switching between T‐cell phenotypes, the effects that the interaction between T and B cells have on one another's cellular metabolism are yet to be understood in disease context. Here, we propose a perspective which highlights the potential of targeting metabolism to modulate T‐ and B‐cell subtypes populations as well as T–B and B–T cell interactions to successfully treat autoimmune disorders. Specifically, we envision how metabolic changes can tip the balance of immune cells interactions, through definite mechanisms in both health and disease, to explain phenotype switches of B and T cells. Within this scenario, we highlight targeting metabolism that link inflammation, immunometabolism, epigenetics and ageing, is critical to understand inflammatory disorders. The combination of treatments targeting immune cells that cause (T/B) cell phenotype imbalances, and the metabolic pathways involved, may increase the effectiveness of treatment of autoimmune disorders, and/or ameliorate their symptoms to improve patients’ quality of life.

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Metabolic regulation of pathogenic autoimmunity: therapeutic targeting

Cited by 29 publications

References 46 publications

Metabolic determinants of lupus pathogenesis

Metabolic determinants of lupus pathogenesis

Immune metabolism regulation of the germinal center response

Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T‐ and B‐cell interactions

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