Targeting Metabolism as a Novel Therapeutic Approach to Autoimmunity, Inflammation, and Transplantation [BRIEF REVIEWS]

Abstract

Immune cell activation and differentiation occurs concurrently with metabolic reprogramming. This ensures that activated cells generate the energy and substrates necessary to perform their specified function. Likewise, the metabolic programs among different cells of the immune system vary. By targeting different metabolic pathways, these differences allow for selective regulation of immune responses. Further, the relative susceptibility of cells to a metabolic inhibitor is dictated by their metabolic demands; cellular selectivity is based on demand. Therefore, where differences exist in metabolic pathways between healthy and pathogenic cells, there is opportunity for selective regulation with agents lacking intrinsic specificity. There are now a host of studies demonstrating how inhibitors of metabolism (e.g., glycolysis, glutamine metabolism, and fatty acid oxidation) can regulate immune responses and treat immune-mediated pathogenesis. In this brief review we detail how inhibitors of metabolism can be employed to regulate immune responses in both autoimmunity and transplantation.

Footnotes

  • This work was supported by National Institutes of Health Grants AI072677, AI77610, and AI09148.

  • Abbreviations used in this article:

    AMPK
    AMP kinase
    BMT
    bone marrow transplantation
    DC
    dendritic cell
    DCA
    dichloroacetate
    2DG
    2-deoxy-glucose
    DON
    6-diazo-5-oxo-l-norleucine
    GVHD
    graft-versus-host disease
    PDH
    pyruvate dehydrogenase
    PDHK
    PDH kinase
    PKM2
    pyruvate kinase M2
    ROS
    reactive oxygen species
    SLE
    systemic lupus erythematosus
    Treg
    regulatory T cell.
  • Received August 2, 2016.
  • Accepted September 20, 2016.

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