Abstract
The autoimmune disorder known as Systemic Lupus Erythematosus (SLE) exhibits intricate features with abnormal immune responses leading to tissue injury. The generation of antibodies and the disruption of immune regulation heavily depend on the pivotal function of T follicular helper (Tfh) cells. Iron dysregulation is significant in autoimmune diseases, impacting immune cell function and disease progression. Our study investigates the role of the HMGA1/EZH2/STAT3/GPX4 axis in modulating Tfh cells and iron homeostasis in SLE. Abnormal Tfh cell populations in SLE patients demonstrate reduced susceptibility to iron-induced cell death, with HMGA1 identified as a key player in Tfh cell proliferation and sensitivity to iron-induced death. Experimental interventions reveal the inhibitory role of the HMGA1 axis in Tfh cells' susceptibility to iron-induced death, suggesting therapeutic avenues for SLE and related autoimmune disorders. Our study underscores the importance of iron homeostasis in autoimmune conditions, providing novel insights and treatment strategies for further research in this field.