Iron plays a critical role in immune responses. However, its role in T helper cell differentiation and function remains poorly understood. In this study, it is shown that the restraint of iron availability through blocking CD71‐mediated iron endocytosis impaired the differentiation and pathogenicity of TH17 cells. Administrations of anti‐CD71 mAb could relieve the development of experimental autoimmune encephalomyelitis (EAE). Mechanistically, the iron deficiency due to the blocking of CD71 enhanced IL‐2 expression, which further restrained the differentiation of TH17 cells. Meanwhile, CD71 blockade impaired histone modifications of Il17 gene and reduced the recruitment of RORγt to Il17a locus. In sum, the findings reveal that iron plays a pivotal role in regulating TH17 cell differentiation and function in autoimmune diseases.

Follicular helper T (TFH) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the TFH differentiation by promoting TFH lineage associated gene expression during acute viral infection, including Tcf7 and Bcl6. By using conditional deletion murine system, we observed that EZH2 ablation in CD4+ T cells was accompanied by aberrant accumulation of DNA methyltransferases (DNMTs) DNMT1 and DNMT3B in TFH cells. And the loss of EZH2 promoted aggravation of DNA methylation status at Tcf7 locus. Therefore, our findings suggested that EZH2 plays an important role in maintenance of hypomethylation at Tcf7 locus thus affecting TFH differentiation during acute viral infection.