First Author | Gao X | Year | 2022 |
Journal | J Clin Invest | Volume | 132 |
Issue | 9 | PubMed ID | 35499082 |
Mgi Jnum | J:338734 | Mgi Id | MGI:7276074 |
Doi | 10.1172/JCI152345 | Citation | Gao X, et al. (2022) Iron-dependent epigenetic modulation promotes pathogenic T cell differentiation in lupus. J Clin Invest 132(9):e152345 |
abstractText | 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 antigen-specific GC response. Iron supplementation contributed to Tfh cell differentiation. In contrast, iron chelation inhibited Tfh cell differentiation. We demonstrated that the miR-21/BDH2 axis drove iron accumulation during Tfh cell differentiation and further promoted Fe2+-dependent TET enzyme activity and BCL6 gene demethylation. Thus, maintaining iron homeostasis might be critical for eliminating pathogenic Th cells and might help improve the management of patients with SLE. |