Insufficient Iron Improves Pristane-Induced Lupus by Promoting Treg Cell Expansion.

Xiaofei Gao,Shuang Lu,Meiling Zheng,Sujie Jia,Longyuan Hu,Ming Zhao,Yang Song

doi:10.3389/fimmu.2022.799331

Abstract

Trace element iron affects T cell biology, but the knowledge about the role of iron in regulating Treg cell expansion is limited. Treg cells play an important role in keeping peripheral T cell tolerance, increasing Treg cell expansion is a promising therapeutic method for SLE. Here we showed that iron deficiency promotes Treg cell expansion by reducing ROS accumulation, improving the disease progression of pristane-induced lupus. Increased oxidative stress inhibits Treg cell differentiation by inducing cell apoptosis. Our data suggest that altering iron metabolism promotes Treg cell expansion by preventing oxidation-induced cell death, which may provide a potential therapeutic strategy for SLE.

Highlights

Systemic lupus erythematosus (SLE) is a chronic complex autoimmune disease characterized by the overproduction of autoantibodies and multiple organ damage
To explore the role of iron deficiency to Treg cell expansion, we treated 3-weeks old female c57/B6 mice with 5 mg/kg low iron diet (LID) for 5 weeks, mice treated with 50 mg/kg normal iron diet (ND) was served as the control group
Consistent with the mRNA expression, the frequency of CD4+CD25+Foxp3+ Treg cells was significantly elevated in the dLNs of LID-treated mice compared with the ND controls, but it has no significant changes in the spleen (Figures 1C, D)

Summary

INTRODUCTION

Systemic lupus erythematosus (SLE) is a chronic complex autoimmune disease characterized by the overproduction of autoantibodies and multiple organ damage. Increased oxidative stress is harmful to cell biologies, such as inducing DNA mutations, iron-dependent lipid oxidization, and cell death. In lupus, increased oxidative stress contributes to Treg cell depletion, suggesting that relieving oxidative stress may be an effective therapeutic method by promoting the differentiation of Treg cells [14]. We investigated the role of insufficient iron in Treg cell expansion and the development of SLE. We found that low iron diet (LID) promoted the expansion of Treg cells and reshaped the Th17/Treg cell ratio, thereby improving the disease progression of pristane-induced lupus. Insufficient iron contributes to Treg cell differentiation by reducing the ROS accumulation, which promotes cell death in Treg cells. Our data show that reducing intracellular iron supports Treg cell expansion in SLE, which suggested a promising therapeutic method for SLE

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT