Yang Liu, Han Xinyan, Wang Mengxue, Zhang Xiaojuan, Wang Lupeng, Xu Nuo, Wu Hui, Shi Hailian, Pan Weidong, Huang Fei, Wu Xiaojun
Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Research (Wash D C). 2025 Apr 15;8:0662. doi: 10.34133/research.0662. eCollection 2025.
Foxp3 regulatory T (T) cells, as one of the subtypes of CD4 T cells, are the crucial gatekeeper in the pathogenesis of self-antigen reactive diseases. In this context, we demonstrated that the selective ablation of early growth response gene 1 (Egr-1) in CD4 T cells exacerbated experimental autoimmune encephalomyelitis (EAE) in murine models. The absence of Egr-1 in CD4 T cells, obtained from EAE mice and naïve CD4 T cells, impeded the differentiation and influence of T. Importantly, in CD4 T cells of multiple sclerosis patients, both Egr-1 and Foxp3 were found to decrease. Further studies showed that distinct from the classical Smad3 route, TGF-β could activate Egr-1 through the Raf-Erk signaling route to promote Foxp3 genetic modulation, thereby promoting T cell differentiation and reducing EAE inflammation. A novel natural Egr-1 agonist, calycosin, was found to attenuate EAE progression by regulating the differentiation of T. Together, the above results indicate the value of Egr-1, as a novel Foxp3 transactivator, for the differentiation of T cells in the development of self-antigen reactive diseases.
叉头框蛋白3调节性T（Treg）细胞作为CD4 T细胞的亚型之一，是自身抗原反应性疾病发病机制中的关键守门人。在此背景下，我们证明了CD4 T细胞中早期生长反应基因1（Egr-1）的选择性缺失会加剧小鼠模型中的实验性自身免疫性脑脊髓炎（EAE）。从EAE小鼠和未致敏的CD4 T细胞中获得的CD4 T细胞中Egr-1的缺失，阻碍了Treg的分化和影响。重要的是，在多发性硬化症患者的CD4 T细胞中，发现Egr-1和Foxp3均减少。进一步的研究表明，与经典的Smad3途径不同，转化生长因子-β（TGF-β）可通过Raf-Erk信号途径激活Egr-1，以促进Foxp3基因调节，从而促进Treg细胞分化并减轻EAE炎症。发现一种新型的天然Egr-1激动剂毛蕊异黄酮通过调节Treg细胞的分化来减轻EAE的进展。综上所述，上述结果表明Egr-1作为一种新型的Foxp3反式激活因子，在自身抗原反应性疾病发展过程中对Treg细胞分化具有重要价值。
