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Lactate-induced metabolic reprogramming was characterized by not only reduced glycolysis but also enhanced de novo fatty acid synthesis in CD4 + T cells with a drop in the NAD + /NADH ratio through the upregulation of the lactate transporter SLC5A12, which reshaped their effector phenotypes, resulting in increased IL17 production via an increase of PKM2 nuclear translocation with concomitant enhanced STAT3 phosphorylation, and induced tissue retention of these pathogenic T cells in rheumatoid arthritis [138, 139]