Metabolic Targets for Treatment of Autoimmune Diseases

Immunometabolism. 2020;2(2):e200012. doi: 10.20900/immunometab20200012. Epub 2020 Mar 31.

Abstract

There is a considerable unmet demand for safe and efficacious medications in the realm of autoimmune and inflammatory diseases. The fate of the immune cells is precisely governed by control of various metabolic processes such as mitochondrial oxidative phosphorylation, glycolysis, fatty acid synthesis, beta-oxidation, amino acid metabolism, and several others including the pentose phosphate pathway, which is a unique source of metabolites for cell proliferation and maintenance of a reducing environment. These pathways are tightly regulated by the cytokines, growth factors, availability of the nutrients and host-microbe interaction. Exploring the immunometabolic pathways that govern the fate of cells of the innate and adaptive immune system, during various stages of activation, proliferation, differentiation and effector response, is crucial for new development of new treatment targets. Identifying the pathway connections and key enzymes will help us to target the dysregulated inflammation in autoimmune diseases. The mechanistic target of rapamycin (mTOR) pathway is increasingly recognized as one of the key drivers of proinflammatory responses in autoimmune diseases. In this review, we provide an update on the current understanding of the metabolic signatures noted within different immune cells of many different autoimmune diseases with a focus on selecting pathways and specific metabolites as targets for treatment.

Keywords: acetylcysteine; glycolysis; immune metabolic pathways; kynurenine; mechanistic target of rapamycin; oxidative phosphorylation; oxidative stress; pentose phosphate pathway; psoriasis; rheumatoid arthritis; scleroderma; systemic lupus erythematosus; tryptophan.