Iron-dependent epigenetic modulation promotes pathogenic T cell differentiation in lupus

The trace element iron affects immune responses and vaccination, but knowledge of its role in autoimmune diseases is limited. Expansion of pathogenic T cells, especially T follicular helper (Tfh) cells, has great significance to systemic lupus erythematosus (SLE) pathogenesis. Here, we show an important role of iron in regulation of pathogenic T cell differentiation in SLE. We found that iron overload promoted Tfh cell expansion, proinflammatory cytokine secretion, and autoantibody production in lupus-prone mice. Mice treated with a high-iron diet exhibited an increased proportion of Tfh cell and antigencell differentiation. We demonstrated that the miR-21/BDH2 axis drove iron accumulation during Tfh cell differentiation and might be critical for eliminating pathogenic Th cells and might help improve the management of patients with SLE.

Automated summary

Iron plays an important role in regulating pathogenic T cell differentiation and autoantibody production in SLE. High-iron diet promotes Tfh cell expansion, and the miR-21/BDH2 axis may be critical for iron accumulation during Tfh cell differentiation.