Metabolism as a Target for Modulation in Autoimmune Diseases. Issue 7 (July 2018)

• Record Type: Journal Article
• Authors: Huang, Nick; Perl, Andras
• Is Part Of: Trends in immunology. Volume 39:Issue 7(2018)
• Page Start: 562
• Page End: 576
• Publication Date: 2018-07
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2018.04.006
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Metabolic pathways are now well recognized as important regulators of immune differentiation and activation, and thus influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanistic target of rapamycin (mTOR) has emerged as a key sensor of metabolic stress and an important mediator of proinflammatory lineage specification. Metabolic pathways control the production of mitochondrial reactive oxygen species (ROS), which promote mTOR activation and also modulate the antigenicity of proteins, lipids, and DNA, thus placing ROS at the heart of metabolic disturbances during pathogenesis of SLE. Therefore, we review here the pathways that control ROS production and mTOR activation and identify targets for safe therapeutic modulation of the signaling network that underlies autoimmune diseases, focusing on SLE. Highlights: Metabolic pathways control lineage specification and function in the immune system and influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). Metabolic demands fluctuate during activation and differentiation: effector T cells and plasma cells primarily rely on glycolysis, while memory and regulatory T cells and memory B cells depend on mitochondrial oxidative phosphorylation. The mechanistic target of rapamycin (mTOR) serves pivotal roles in sensing metabolic, immune receptor, and gene expression cues and regulating proliferation, survival, and autophagy in cell type-specific manners. Proinflammatory lineage skewing involves the accumulation of oxidative-stress-generating mitochondria, mTOR activation and increased glycolysis, thus offering metabolic targets for immunomodulation in SLE and other autoimmune diseases.