Hradilkova K, Maschmeyer P, Westendorf K, et al. - Researchers sought to determine the metabolic adaptation of CD4+ T helper lymphocytes that persist over time in inflamed tissue, which has low availability of oxygen and nutrients. They stimulated either once or repeatedly the synovial and blood CD4+ T cells isolated ex vivo from patients with juvenile idiopathic arthritis (JIA) and murine CD4+ T cells. Using pharmacologic inhibitors, analysis of their dependency on particular metabolic pathways for survival was done. They determined lactate production and oxygen consumption in Twist1-sufficient and Twist1-deficient murine T cells to assess the role of the transcription factor Twist 1. Pharmacologic inhibitors were used to determine the dependency of these murine cells on particular metabolic pathways. Via fatty acid oxidation (mean ± SEM survival of 3.4 ± 2.85% in the presence of etomoxir vs 60 ± 7.08% in the absence of etomoxir on day 4 of culture), survival of programmed death 1 (PD-1)+ T helper cells in synovial fluid samples from patients with JIA was identified. Further, these cells expressed the E-box–binding transcription factor Twist1 (2–14-fold increased expression) (P = 0.0156 vs PD-1− T helper cells; n = 6). Findings emphasize the value of Twist1 as a master regulator of metabolic adaptation of T helper cells to chronic inflammation and suggest it as a target for their selective therapeutic elimination.