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Review
. 2019 May:109:81-87.
doi: 10.1016/j.molimm.2019.03.005. Epub 2019 Mar 20.

Metabolic regulation of TH17 cells

Hongxing Shen  1 , Lewis Zhichang Shi  2
Affiliations
Review

Metabolic regulation of TH17 cells

Hongxing Shen et al. Mol Immunol. 2019 May.

Abstract

IL-17-producing TH17 cells have been associated with autoimmune diseases such as multiple sclerosis (MS), psoriasis, Crohn's disease, and ulcerative colitis (Han et al., 2015), many of which lack effective therapies. Identifying effective approaches to selectively suppress TH17 cell development and function represents a legitimate strategy to cure these autoimmune disorders. TH17 cell differentiation requires rewiring of their metabolic program, transition from the oxidative phosphorylation-dominant catabolic phenotype in quiescent naïve T cells to glucose metabolism-orchestrated anabolic phenotype including lipogenesis. Here, we provide a focused review on the glycolytic-lipogenic pathway in TH17 development and pathogenicity. These studies reveal several metabolic checkpoints with specific regulation of TH17 cells (but not other T cell lineages), manifesting potential therapeutic opportunities to TH17 cell-mediated autoimmune diseases.

Keywords: Fatty acid synthesis; Glycolysis; HIF1α; T(H)17; mTOR.

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Figures

Fig. 1.
Fig. 1.. The glycolytic-lipogenic pathway in TH17 cells.
HK2: hexokinase 2; PKM2: pyruvate kinase muscle isozyme M2; LDHa: lactate dehydrogenase A; PDH: pyruvate dehydrogenase; PDHK1: pyruvate dehydrogenase kinase 1; ACC1: acetyl-CoA carboxylase 1; FASN: fatty acid synthase; HMGCR: 3-hydroxy-3-methylglutaryl CoA reductase. Metabolic enzymes highlighted in blue are the ones that have been shown to be involved in TH17 differentiation and function. Solid arrows indicate single-step reactions; dashed arrows indicate multiple steps involved (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
See this image and copyright information in PMC

References

    1. Angajala A, Lim S, Phillips JB, Kim JH, Yates C, You Z, Tan M, 2018. Diverse roles of mitochondria in immune responses: novel insights into immuno-metabolism. Front. Immunol 9, 1605. - PMC - PubMed
    1. Annunziato F, Cosmi L, Liotta F, Maggi E, Romagnani S, 2009. Human Th17 cells: are they different from murine Th17 cells? Eur. J. Immunol 39, 637–640. - PubMed
    1. Barbi J, Pardoll D, Pan F, 2013. Metabolic control of the Treg/Th17 axis. Immunol. Rev 252, 52–77. - PMC - PubMed
    1. Berod L, Friedrich C, Nandan A, Freitag J, Hagemann S, Harmrolfs K, Sandouk A, Hesse C, Castro CN, Bahre H, Tschirner SK, Gorinski N, Gohmert M, Mayer CT, Huehn J, Ponimaskin E, Abraham WR, Muller R, Lochner M, Sparwasser T, 2014. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat. Med 20, 1327–1333. - PubMed
    1. Bottcher M, Renner K, Berger R, Mentz K, Thomas S, Cardenas-Conejo ZE, Dettmer K, Oefner PJ, Mackensen A, Kreutz M, Mougiakakos D, 2018. D-2-hydroxyglutarate interferes with HIF-1alpha stability skewing T-cell metabolism towards oxidative phosphorylation and impairing Th17 polarization. Oncoimmunology 7, e1445454. - PMC - PubMed

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