Zhao Shan, Chen Xiaotong, Chang Bohan, Tian Bailing
Department of Rheumatology and Immunology, The First Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Cell Biol Toxicol. 2024 Dec 21;41(1):6. doi: 10.1007/s10565-024-09955-5.
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.
被称为系统性红斑狼疮（SLE）的自身免疫性疾病具有复杂的特征，其异常的免疫反应会导致组织损伤。抗体的产生和免疫调节的破坏在很大程度上依赖于滤泡辅助性T（Tfh）细胞的关键功能。铁调节异常在自身免疫性疾病中很重要，会影响免疫细胞功能和疾病进展。我们的研究调查了HMGA1/EZH2/STAT3/GPX4轴在调节SLE中Tfh细胞和铁稳态方面的作用。SLE患者中异常的Tfh细胞群体对铁诱导的细胞死亡敏感性降低，HMGA1被确定为Tfh细胞增殖和对铁诱导死亡敏感性的关键因素。实验干预揭示了HMGA1轴在Tfh细胞对铁诱导死亡的易感性中的抑制作用，为SLE和相关自身免疫性疾病提供了治疗途径。我们的研究强调了铁稳态在自身免疫性疾病中的重要性，为该领域的进一步研究提供了新的见解和治疗策略。
