This research seeks to explore the intricate relationship between immune cell metabolism and the pathogenesis of autoimmune diseases. While immune responses are typically studied through the lens of cytokine production and immune cell signaling, recent studies suggest that metabolic changes in immune cells may play a critical role in regulating immune function and influencing disease outcomes.
The question at hand is whether metabolic reprogramming in T cells, B cells, and other immune cell types can exacerbate or mitigate autoimmune responses. By investigating how shifts in metabolic pathways, such as glycolysis, oxidative phosphorylation, and lipid metabolism, affect immune cell activation and differentiation, this research aims to uncover potential therapeutic targets for treating autoimmune diseases. Understanding how immune cell metabolism interacts with inflammatory processes could open new avenues for personalized treatment strategies in autoimmune diseases like rheumatoid arthritis, lupus, and multiple sclerosis
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From a 2017 clinical investigation, Lim et al. reported how activation of the kynurenine pathway (KP) (i.e tryptophan metabolism) causes an imbalance of two key metabolites, kynurenic acid (KA) and quinolinic acid (QA). This may lead to overactivation of the N-methyl-D-Aspartate (NMDA) receptor. Dysfunction of this receptor is associated with the relapse and progression of autoimmune-associated neurological disorders such as multiple sclerosis (MS).
A contributor to the pathology of the disease was found to be due to increased expression of the innate immunity signature proteins, macrophage inflammatory protein (MIP)-1α, leading to macrophage infiltration. QA production by these macrophages contributes to oligodendrocyte death.
A clinical focus on modulation of the KP may be of therapeutic value in preventing relapses or slowing progression.
Lim, Chai K., Ayse Bilgin, David B. Lovejoy, Vanessa Tan, Sonia Bustamante, Bruce V. Taylor, Alban Bessede, Bruce J. Brew, and Gilles J. Guillemin. ‘Kynurenine Pathway Metabolomics Predicts and Provides Mechanistic Insight into Multiple Sclerosis Progression’. Scientific Reports 7, no. 1 (3 February 2017): 41473. https://doi.org/10.1038/srep41473.
Sundaram, Gayathri, Chai K. Lim, Bruce J. Brew, and Gilles J. Guillemin. ‘Kynurenine Pathway Modulation Reverses the Experimental Autoimmune Encephalomyelitis Mouse Disease Progression’. Journal of Neuroinflammation 17, no. 1 (6 June 2020): 176. https://doi.org/10.1186/s12974-020-01844-y.
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