CD4 and autoimmune disease: IL-21 is produced mostly by activated CD4+ T cells and controls the differentiation and functional activity of effector TH cells,[14] whereas a high level of IL–21 triggers the inflammatory pathway and promotes tissue damage in some autoimmune diseases.[22–25] A study by Ge et al[26] reported that elevated intracellular IL-21 was correlated to the TH17 cell proportion in UC patients, suggesting that IL-21 is mainly produced by TH17 cells in UC.