Extended Data Fig. 10: The hypothetical model for neutrophil ferroptosis in SLE pathogenesis.
From: Glutathione peroxidase 4–regulated neutrophil ferroptosis induces systemic autoimmunity
Autoantibodies and interferon-α present in SLE sera enhance binding of the transcriptional repressor CREMα to Gpx4 promoter, which leads to suppressed expression of GPX4 and subsequent elevation of lipid-ROS. These lead to neutrophil ferroptosis and further promote SLE progression in patients. Moreover, mice with neutrophil-specific Gpx4 haploinsufficiency develop lupus phenotype and inhibition of neutrophil ferroptosis significantly mitigates disease development in lupus-prone mice.
