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. 2020;2(2):e200009.
doi: 10.20900/immunometab20200009. Epub 2020 Feb 10.

T cell Metabolism in Lupus

Milena Vukelic  1 , Michihito Kono  2 , George C Tsokos  1
Affiliations

T cell Metabolism in Lupus

Milena Vukelic et al. Immunometabolism. 2020.

Abstract

Abnormal T cell responses are central to the development of autoimmunity and organ damage in systemic lupus erythematosus. Following stimulation, naïve T cells undergo rapid proliferation, differentiation and cytokine production. Since the initial report, approximately two decades ago, that engagement of CD28 enhances glycolysis but PD-1 and CTLA-4 decrease it, significant information has been generated which has linked metabolic reprogramming with the fate of differentiating T cell in health and autoimmunity. Herein we summarize how defects in mitochondrial dysfunction, oxidative stress, glycolysis, glutaminolysis and lipid metabolism contribute to pro-inflammatory T cell responses in systemic lupus erythematosus and discuss how metabolic defects can be exploited therapeutically.

Keywords: SLE; T cell metabolism; fatty acid oxidation; glutaminolysis; glycolysis.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Main metabolic pathways in T cells. Cellular metabolism is controlled by many factors, including transcription factors. Red arrow means “enhance or activate”, whereas blue line means “inhibit or inactivate”. Acetyl Co-A, acetyl coenzyme A; mTOR, mammalian target of rapamycin; AMPK, adenosine monophosphate activated protein kinase; HIF-1α, hypoxia inducible factor 1 alpha; PKM2, pyruvate kinase muscle isozyme 2; CaMK4, calcium/calmodulin–dependent protein kinase IV; PDH, pyruvate dehydrogenase; ICER, inducible cAMP early repressor; α-KG, α-ketoglutarate; ETC, electron transport chain; OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species.
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