Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are relatively common autoimmune diseases, often considered prototypic examples for how protective immunity switches to destructive immunity. The autoantigens recognized in RA and SLE are distinct, clinical manifestations are partially overlapping. A shared feature is the propensity of the adaptive immune system to respond inappropriately, with T cell hyper-responsiveness a pinnacle pathogenic defect. Upon antigen recognition, T cells mobilize a multi-pranged metabolic program, enabling them to massively expand and turn into highly mobile effector cells. Current evidence supports that T cells from patients with RA or SLE adopt metabolic programs different from healthy T cells, in line with the concept that autoimmune effector functions rely on specified pathways of energy sensing, energy generation and energy utilization. Due to misrouting of the energy sensor AMPK, RA T cells have a defect in balancing catabolic and anabolic processes and deviate towards a cell-building program. They supply biosynthetic precursors by shunting glucose away from glycolytic breakdown towards the pentose phosphate pathway and upregulate lipogenesis, enabling cellular motility and tissue invasiveness. Conversely, T cells from SLE patients are committed to high glycolytic flux, overusing the mitochondrial machinery and imposing oxidative stress. Typically, disease-relevant effector functions in SLE are associated with inappropriate activation of the key metabolic regulator mTORC1. Taken together, disease-specific metabolic signatures in RA and SLE represent vulnerabilities that are therapeutically targetable to suppress pathogenic immune responses.
Keywords: T cells; glucose; glycolysis; lipid droplets; lipogenesis; mitochondria; oxygen consumption; rheumatoid arthritis; systemic lupus erythematosus.