These key differences in metabolic rewiring have led to the identification of several potential therapeutic targets, some of which are currently being tested in clinical trials, that are orthogonal to the standard of care for SLE based on steroidal and nonsteroidal immunosuppressants . These include a combination therapy of 2-deoxy-D-glucose (2DG) and metformin that inhibit the first step of glycolysis and mitochondrial activity, respectively , and inhibition of glutaminase, the first enzyme in glutaminolysis , in lupus-prone mice. Supplementation with N-acetyl cysteine, a reducing agent that is a precursor of cysteine, an amino acid used in glutathione synthesis, and treatment with mTOR inhibitor sirolimus or with metformin, have also shown promising results in SLE patients . The overarching goal to use cellular metabolism to selectively dampen the inflammatory autoreactive immune cells in SLE mirrors a growing effort to activate exhausted immune cells in the tumor microenvironment also through metabolic reprogramming . A need for system-wide study of metabolic changes Several genetic, signaling, and metabolic investigations suggest that there are large-scale differences in the metabolism of HC and SLE T cells . However, most previous works, including those cited above, have studied metabolic pathways and nutrients in isolation, often using only one approach (e.g. metabolomics or transcriptomics) or one metabolic pathway (e.g. glycolysis). Importantly, however, the human metabolic network simultaneously carries out thousands of interdependent chemical conversions , with in-built large-scale dependencies and compensation mechanisms. Moreover, metabolic reactions are governed by tight constraints imposed by mass and energy balance as well as the laws of thermodynamics . Therefore, the exchange of nutrients and waste products and their relationship with cell proliferation and the cellular metabolic state must be understood simultaneously.