A Promising Therapeutic Target for Autoimmune Diseases Like Multiple Sclerosis
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A Promising Therapeutic Target for Autoimmune Diseases Like Multiple Sclerosis


Researchers reveal how activating the Egr-1 gene can help alleviate autoimmune inflammation via Foxp3 expression

Autoimmune diseases, like multiple sclerosis result when the body’s immune system starts to attack its own cells. Regulatory T cells, a subtype of T cells play a critical role in suppressing these attacks. Now, a study published in Research (SPJ) sheds light on the potential role of the Egr-1 gene in promoting these protective cells through the activation of the Foxp3 protein. This finding unlocks promising avenues for managing autoimmune conditions via Egr-1 activation.

Autoimmune diseases, such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA), affect millions of people worldwide. These conditions arise when the body’s immune system fails to distinguish between “self” and “foreign” cells, and mistakenly attacks its own healthy cells, resulting in persistent inflammation and tissue damage. Central to these autoimmune responses are CD4+ T cells, a class of immune cells that can either promote or suppress the condition.

Regulatory T cells (Treg) are a special subtype of CD4+ T cells that act as the immune system’s peacekeepers. Treg cells, marked by protein Foxp3, help in suppressing harmful immune responses. However, when the function of Treg cells is compromised, as seen in cases of MS and IBD, the immune response is dominated by the Th1 and Th17 cells (other CD4+T cell subtypes), which promote inflammation, further worsening the disease symptoms. Therefore, boosting the development and activity of Treg cells is emerging as a promising therapeutic approach, but the mechanisms underlying its effective regulation remain unclear.

In pursuit of a deeper understanding of these mechanisms, a team of Chinese scientists led by Dr. Xiaojun Wu and Dr. Fei Huang from the Shanghai Key Laboratory of Compound Chinese Medicines, SHUTCM, China, and Dr. Weidong Pan from the Department of Neurology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China, explored the role of Early Growth Response Gene 1 (Egr-1) in promoting the activity of Treg cells. The study was conducted in a well-established animal model of MS, called experimental autoimmune encephalomyelitis (EAE), to confirm the mechanisms. The findings of this study were published in Volume 8 of Research on April 15, 2025.

Elaborating more, Dr. Wu, the lead author of this study, says “We started by screening the genes that appeared different between mice with mild and severe EAE.” Further, he adds, “Among the top identified genes in CD4+ T cells, Egr-1 stood out as significantly downregulated in severe disease.”

After identifying Egr-1 as a regulatory gene, the team assessed its role by using genetically engineered mice lacking Egr-1 in CD4+ T cells. These mice were induced with EAE and tracked for disease progression. The researchers also analyzed the immune cell compositions in the spleen, lymph nodes, and central nervous system of these mice.

The mice lacking Egr-1 showed worse disease, fewer Treg cells, and more inflammatory TH17 and TH1 cells” explains Dr. Huang.

The researchers also conducted additional in vitro experiments. By analyzing isolated human CD4+ T cells from MS patients and healthy donors, they confirmed that both Egr-1 and Foxp3 levels were reduced in patient samples. Further, to determine whether Egr-1 directly regulates Foxp3, the researchers used chromatin immunoprecipitation, which revealed that Egr-1 binds to the Foxp3 promoter. Additionally, using luciferase reporter assays, they also confirmed that Egr-1 binding increases Foxp3 gene activity. They then traced the pathway to TGF-β (Transforming Growth Factor Beta) signaling via the Raf/Mek/Erk cascade, which activates Egr-1.

We identified a unique mechanism of Egr-1,” explains Dr. Pan, “First, TGF-β activates the Raf/Mek/Erk cascade, which activates Egr-1. Egr-1 then directly binds to the Foxp3 promoter to enhance its expression, bypassing the classical Smad3-dependent pathway.”

What’s more, the researchers also investigated the effect of a natural compound, Calycosin, which acts as an Egr-1 agonist. Treatment with calycosin restored Treg cell functions and improve clinical outcomes in mice with EAE, but only in those with functional Egr-1.

Overall, the study underscores the essential role of Egr-1 in Treg cell development and function, identifying it as a central molecular switch in immune regulation. By elucidating its mechanism and validating the effect of a natural Egr-1 agonist, the study suggests that targeting Egr-1 may offer a promising treatment strategy, potentially transforming therapeutic approaches to autoimmune diseases.
About Shanghai Key Laboratory of Compound Chinese Medicines
The Shanghai Key Laboratory of Compound Chinese Medicines (also known as the Shanghai Municipal Key Laboratory for Compound TCM) is part of the Shanghai University of Traditional Chinese Medicine. It was established in 1999 and accredited in 2001. It is led by Professor Zhengtao Wang, with academicians Hu Zhibi and Chen Kaixian as advisors. The lab integrates modern science with traditional Chinese formulations, developing analytical and bio‑tech platforms to study active compounds, mechanisms, and quality control. It supports drug modernization, industrial collaboration, talent training, and has earned national and local awards.
Website: https://zys.shutcm.edu.cn/1063/list.htm

The complete study is accessible DOI: 10.34133/research.0662

About Research by Science Partner Journal
Launched in 2018, Research is the first journal in the Science Partner Journal (SPJ) program. Research is published by the American Association for the Advancement of Science (AAAS) in association with Science and Technology Review Publishing House. Research publishes fundamental research in the life and physical sciences as well as important findings or issues in engineering and applied science. The journal publishes original research articles, reviews, perspectives, and editorials. IF=10.7, Citescore=13.3.

Funding information
This study was supported by the National Key Research and Development Program (2022YFC3501701), National Natural Science Foundation of China (82374065, 82074043, and 82104425), Eastern Talent Plan Leading Project (BJKJ 2024040), Shanghai Science and Technology Commission 2024 Science and Technology Innovation Action Plan Medical Innovation research field project (24Y12800900), Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine (2023Y ZZ02), and Opening Project of Shanghai Key Laboratory of Compound Chinese Medicines (2023OPCCMSHUTCM-01).
Title: Early Growth Response Gene 1 Benefits Autoimmune Disease by Promoting Regulatory T Cell Differentiation as a Regulator of Foxp3
Authors: Liu Yang, Xinyan Han, Mengxue Wang, Xiaojuan Zhang, Lupeng Wang, Nuo Xu, Hui Wu, Hailian Shi, Weidong Pan, [...] , and Xiaojun Wu
Journal: Research 15 Apr 2025 Vol 8 Article ID: 0662
DOI: 10.34133/research.0662
Attached files
  • In this study, researchers from China have identified that Egr-1 is a key regulatory gene that promotes the activity of Treg via Foxp3 activation, paving way towards the advancement of Treg therapies.
Regions: Asia, China
Keywords: Health, Medical, Public Dialogue - health, Well being, Science, Life Sciences

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