Metabolic Factors that Contribute to Lupus Pathogenesis

Li, Wei; Sivakumar, Ramya; Titov, Anton A.; Choi, Seung‐Chul; Morel, Laurence

doi:10.1615/critrevimmunol.2016017164

Cited by 30 publications

(22 citation statements)

References 232 publications

(292 reference statements)

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“…Defective phagocytic ability, surface marker expression and cytokine production by both macrophages and monocytes were demonstrated in SLE [113,115]. Type 1 interferon signature is increased in monocytes and macrophages in SLE [113].…”

Section: Monocyte Metabolic Profile/signatures In Autoimmune Diseasesmentioning

confidence: 98%

“…However, metabolic changes differ according to the macrophage phenotype. M1 macrophages use glycolysis as their primary energy source and M2 macrophage use OXPHOS as primary source for long and sustained response [112,113]. increased glucose utilization and cytokine production as compared to healthy controls and GCA patients [114].…”

Section: Monocyte Metabolic Profile/signatures In Autoimmune Diseasesmentioning

confidence: 99%

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Metabolic Targets for Treatment of Autoimmune Diseases

2020

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There is a considerable unmet demand for safe and efficacious medications in the realm of autoimmune and inflammatory diseases. The fate of the immune cells is precisely governed by control of various metabolic processes such as mitochondrial oxidative phosphorylation, glycolysis, fatty acid synthesis, beta-oxidation, amino acid metabolism, and several others including the pentose phosphate pathway, which is a unique source of metabolites for cell proliferation and maintenance of a reducing environment. These pathways are tightly regulated by the cytokines, growth factors, availability of the nutrients and host-microbe interaction. Exploring the immunometabolic pathways that govern the fate of cells of the innate and adaptive immune system, during various stages of activation, proliferation, differentiation and effector response, is crucial for new development of new treatment targets. Identifying the pathway connections and key enzymes will help us to target the dysregulated inflammation in autoimmune diseases. The mechanistic target of rapamycin (mTOR) pathway is increasingly recognized as one of the key drivers of proinflammatory responses in autoimmune diseases. In this review, we provide an update on the current understanding of the metabolic signatures noted within different immune cells of many different autoimmune diseases with a focus on selecting pathways and specific metabolites as targets for treatment.

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Section: Monocyte Metabolic Profile/signatures In Autoimmune Diseasesmentioning

confidence: 98%

Section: Monocyte Metabolic Profile/signatures In Autoimmune Diseasesmentioning

confidence: 99%

Metabolic Targets for Treatment of Autoimmune Diseases

2020

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“…There is increasing appreciation that heightened glucose metabolism of autoreactive lymphocytes is an intrinsic property of multiple autoimmune disorders, including but not limited to systemic lupus erythematous (SLE) and rheumatoid arthritis . This realization is based on findings that inhibitors of glucose metabolism show efficacy in a variety of autoimmune mouse models and in humans …”

Section: Introductionmentioning

confidence: 99%

2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

Sundberg

Silva

Kennedy

et al. 2019

Experimental Dermatology

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2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.

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“…Other substrates, such as fatty acids via β-oxidation (also called fatty acid oxidation [FAO]), can replenish the TCA cycle to fuel OXPHOS 10 . In addition to substrates used for energy production and de novo biosynthesis, mitochondrial metabolic pathways (such as the TCA, FAO, or OXPHOS) provide substrates for epigenetic modifications of DNA and histones 11, 12 . This is the case, for instance, of acetyl-CoA for histone acetylation, which is associated with active transcription 11 .…”

Section: Introductionmentioning

confidence: 99%

“…This is the case, for instance, of acetyl-CoA for histone acetylation, which is associated with active transcription 11 . This connects mitochondrial metabolism to epigenetic regulation 12 . This specific aspect will be briefly discussed in the Conclusions of this article.…”

Section: Introductionmentioning

confidence: 99%

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

Saas¹,

Varin²,

Perruche³

et al. 2017

F1000Res

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There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors ( i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

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Metabolic Factors that Contribute to Lupus Pathogenesis

Cited by 30 publications

References 232 publications

Metabolic Targets for Treatment of Autoimmune Diseases

Metabolic Targets for Treatment of Autoimmune Diseases

2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

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