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Review
. 2022 Oct:78:102245.
doi: 10.1016/j.coi.2022.102245. Epub 2022 Sep 16.

Immunometabolic alterations in lupus: where do they come from and where do we go from there?

Longhuan Ma  1 , Tracoyia Roach  1 , Laurence Morel  2
Affiliations
Review

Immunometabolic alterations in lupus: where do they come from and where do we go from there?

Longhuan Ma et al. Curr Opin Immunol. 2022 Oct.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the overactivation of the immune system has been associated with metabolic alterations. Targeting the altered immunometabolism has been proposed to treat SLE patients based on their results obtained and mouse models of the disease. Here, we review the recent literature to discuss the possible origins of the alterations in the metabolism of immune cells in lupus, the dominant role of mitochondrial defects, technological advances that may move the field forward, as well as how targeting lupus immunometabolism may have therapeutic potential.

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Figures

Figure 1.
Figure 1.. Origins of immunometabolic alterations in lupus.
Multiple factors contribute to the immunometabolic alterations in lupus, including immune activation (A), chronic activation by autoantigens (B), genetic variation (C) and microbial dysbiosis (D).
Figure 2.
Figure 2.. Mitochondria are a central hub for metabolic alterations in lupus.
Recent studies have uncovered novel contributions from mitochondrial metabolism to lupus pathogenesis. (A) Mitochondria-loaded RBCs triggers type I IFN production in macrophages after phagocytosis. (B) An hyperoxidative state promotes the production of isoLGs adducts that decrease C1q expression, which compromises apoptotic cell clearance and accumulates anti-isoLGs immune complexes. (C) High expression of CD38 reduces NAD+ levels in CD8+ T cells, which impairs their mitochondrial integrity and their cytotoxic function. (D) miR-21 driven intracellular accumulation in CD4+ T cells promotes Tfh cell differentiation by increasing BCL6 expression.
Figure 3.
Figure 3.. Novel approaches to study immunometabolism that may be used in lupus.
Single cell metabolomics, transcriptomics, or a combination of the two, as well as CRISPR screens have been performed for unbiased discovery of metabolic pathways in healthy immune cells.
Figure 4.
Figure 4.
Potential therapeutic targets identified by the analysis of immunometabolism alterations in lupus.
See this image and copyright information in PMC

References

    1. Morel L: Immunometabolism in systemic lupus erythematosus. Nat Rev Rheumatol 2017, 13:280–290. - PubMed
    1. Vukelic M, Kono M, Tsokos GC: T cell metabolism in lupus. Immunometabolism 2020, 2. - PMC - PubMed
    1. Perl A: Review: Metabolic control of immune system activation in rheumatic diseases. Arthritis Rheumatol 2017, 69:2259–2270. - PMC - PubMed
    1. Teng X, Cornaby C, Li W, Morel L: Metabolic regulation of pathogenic autoimmunity: therapeutic targeting. Curr Opin Immunol 2019, 61:10–16. - PMC - PubMed
    1. Piranavan P, Bhamra M, Perl A: Metabolic targets for treatment of autoimmune diseases. Immunometabolism 2020, 2. - PMC - PubMed

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