Early Growth Response Gene 1 Benefits Autoimmune Disease by Promoting Regulatory T Cell Differentiation as a Regulator of Foxp3

  • Research (Wash D C). 2025 Apr 15:8:0662. doi: 10.34133/research.0662.
Liu Yang  1  2 ,  Xinyan Han  1  3 ,  Mengxue Wang  1 ,  Xiaojuan Zhang  1 ,  Lupeng Wang  1 ,  Nuo Xu  1 ,  Hui Wu  1 ,  Hailian Shi  1 ,  Weidong Pan  4 ,  Fei Huang  1 ,  Xiaojun Wu  1
Affiliations
  • 1. 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.
  • 2. Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 3. Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi'an, China.
  • 4. Department of Neurology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PMID: 40235598 DOI: 10.34133/research.0662
Abstract

Foxp3+ regulatory T (Treg) 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 Treg. 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 Treg cell differentiation and reducing EAE inflammation. A novel natural Egr-1 agonist, calycosin, was found to attenuate EAE progression by regulating the differentiation of Treg. Together, the above results indicate the value of Egr-1, as a novel Foxp3 transactivator, for the differentiation of Treg cells in the development of self-antigen reactive diseases.

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