SLC7A11 deficiency exacerbates systemic lupus erythematosus by inducing instability and ferroptosis in regulatory T cells
- 1Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College
- 2Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital, Central South University
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease posing a significant threat to human health. Regulatory T cells (Tregs) are crucial for immune homeostasis. Dysfunction of Tregs have been demonstrated in SLE, but underlying mechanisms remain largely unclear. Here, we observe that peripheral Treg numbers and SLC7A11 expression in Tregs are reduced in SLE, with SLC7A11 levels negatively correlates with disease activity. Treg-specific SLC7A11 deletion impairs their stability and differentiation, promotes a pro-inflammatory phenotype, thereby aggravating autoantibody production and lupus progression in mice. Mechanistically, mild SLC7A11 inhibition stabilizes HIF-1α, enhances glycolysis and increases pro-inflammatory cytokines in Tregs. Severe SLC7A11 inhibition causes excessive lipid peroxidation and ferroptosis. In summary, our findings suggest that SLE Tregs with reduced SLC7A11 expression may undergo varying degrees of damage. Specifically, mild SLC7A11 deficiency drives glycolysis and Treg instability, whereas severe deficiency triggers ferroptosis. Upregulating SLC7A11 expression may be a promising therapeutic strategy for SLE.
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BibTeX
@article{ouyang2026slc7a11,
title = {{SLC7A11 deficiency exacerbates systemic lupus erythematosus by inducing instability and ferroptosis in regulatory T cells}},
author = {Lianlian Ouyang and Fangqi Chen and Meiling Zheng and Zhi Hu and Xiaoli Min and Yang Song and Xiaofei Gao and Xiaoyun Chen and Qiaolin Wang and Qianjin Lu and Ming Zhao},
journal = {Communications Biology},
year = {2026},
month = jun,
doi = {10.1038/s42003-026-10570-9},
url = {https://doi.org/10.1038/s42003-026-10570-9},
note = {CC BY},
}
RIS
TY - JOUR
TI - SLC7A11 deficiency exacerbates systemic lupus erythematosus by inducing instability and ferroptosis in regulatory T cells
AU - Lianlian Ouyang
AU - Fangqi Chen
AU - Meiling Zheng
AU - Zhi Hu
AU - Xiaoli Min
AU - Yang Song
AU - Xiaofei Gao
AU - Xiaoyun Chen
AU - Qiaolin Wang
AU - Qianjin Lu
AU - Ming Zhao
PY - 2026
DA - 2026/06/01
JO - Communications Biology
DO - 10.1038/s42003-026-10570-9
UR - https://doi.org/10.1038/s42003-026-10570-9
AB - Systemic lupus erythematosus (SLE) is an autoimmune disease posing a significant threat to human health. Regulatory T cells (Tregs) are crucial for immune homeostasis. Dysfunction of Tregs have been demonstrated in SLE, but underlying mechanisms remain largely unclear. Here, we observe that peripheral Treg numbers and SLC7A11 expression in Tregs are reduced in SLE, with SLC7A11 levels negatively correlates with disease activity. Treg-specific SLC7A11 deletion impairs their stability and differentiation, promotes a pro-inflammatory phenotype, thereby aggravating autoantibody production and lupus progression in mice. Mechanistically, mild SLC7A11 inhibition stabilizes HIF-1α, enhances glycolysis and increases pro-inflammatory cytokines in Tregs. Severe SLC7A11 inhibition causes excessive lipid peroxidation and ferroptosis. In summary, our findings suggest that SLE Tregs with reduced SLC7A11 expression may undergo varying degrees of damage. Specifically, mild SLC7A11 deficiency drives glycolysis and Treg instability, whereas severe deficiency triggers ferroptosis. Upregulating SLC7A11 expression may be a promising therapeutic strategy for SLE.
SN - 2399-3642
ER -