Therapeutic perspectives on the metabolism of lymphocytes in patients with rheumatoid arthritis and systemic lupus erythematosus

The activation of autoreactive T- and B-cells and production of autoantibodies by B cells are involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recently, the concept of 'immunometabolism' has attracted significant attention. Immune cells produce large amounts of energy in the form of ATP and biosynthesize biological components such as nucleic acids and lipids via metabolic reprogramming to activate, differentiate, and exert their functions.While the mechanisms underlying the metabolism of CD4+ T cells in SLE have been extensively studied, the metabolic changes underlying B cell activation, differentiation, and function remain unclear. Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs. In this review, we summarize the current knowledge on the immunometabolic mechanisms involved in SLE and RA and discuss the potential novel therapeutic drugs.The intensity of activation of different immune cells and their metabolic kinetics vary in different autoimmune diseases; thus, understanding the disease- and cell-specific metabolic mechanisms may help in the development of clinically effective immunometabolism-targeting drugs.