Indeed, accumulated lactic acid supports pro-inflammatory T cells to remain at the double-positive stage and produce more IL-17 (144, 145), while ROS causes oxidation with broad impacts (116, 117); however, as discussed above, in CD4+ T cells at the preliminary stages of RA, glycolysis is decreased and ROS is exhausted, resulting in a reductive metabolic microenvironment (low pyruvate and high NADPH) and triggering aberrant lipogenesis. Here, CD4 is linked to rheumatoid arthritis.