Modifying iron metabolism to mitigate oxidative stress and rebalance the Th17/Treg cell ratio in systemic lupus erythematosus (SLE) may represent a promising therapeutic target for treating SLE.
Methodology
We used the iron chelator deferoxamine mesylate (DFO) and a low iron diet (LID) to treat imiquimod (IMQ)-induced lupus-like syndrome in mice. We observed the changes in T lymphocytes and iron metabolism in the spleen. Splenic naive CD4+T cells were induced to differentiate into Th17 and Treg cells through magnetic separation and were cultured with DFO solution to observe the effect of DFO on the balance of Th17/Treg cells. Ras-selective lethal3 (RSL3)-induced ferroptosis in Naïve CD4+T cells was treated with DFO.
Major Findings
We found that iron deficiency may promote the expansion of Treg cells and suppress the production of Th17 cells by activating the Nrf2/HO-1/GPX4 signaling pathway, reducing the accumulation of reactive oxygen species (ROS), and thus halting the progression of IMQ-induced lupus-like disease.
Conclusion
Iron deficiency, both in vitro and in vivo, inhibited the inflammatory response, reducing the production of inflammatory cytokines. This could present a possible therapeutic approach for SLE.
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