中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3267-3280.doi: 10.4103/NRR.NRR-D-24-01646

• 原著:退行性病与再生 • 上一篇    

干扰素调节因子1增强重症肌无力T细胞的分化

  

  • 出版日期:2026-07-15 发布日期:2026-04-01

Interferon regulatory factor 1 enhances T cell differentiation in myasthenia gravis

Yuebei Luo1, 2, 3, 4, Yijun Ren1, 4, Zeyi Wen1, 4, Zhaohui Luo1, 3, 4, Huan Yang1, 2, 3, 4, Liqun Xu1, 2, 3, 4, *   

  1. 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 
    2Department of Neurology, Xiangya Hospital, Central South University, Jiangxi (National Regional Center for Neurological Diseases), Nanchang, Jiangxi Province, China; 
    3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 
    4Research Center for Neuroimmune and Neuromuscular Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Online:2026-07-15 Published:2026-04-01
  • Contact: Liqun Xu, MD, 404608@csu.edu.cn.
  • Supported by:
    This study was supported by a grant from the National Natural Science Foundation of China, No. 82271440; and Jiangxi Provincial Health Technology Project, No. 202510009 (both to LX).

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摘要：

干扰素调节因子1在多种自身免疫性疾病中具有重要意义，且在重症肌无力患者中高表达，但其作用机制尚不可知。此次实验旨在探索干扰素调节因子1在重症肌无力中的作用，并了解其潜在机制。研究纳入具有乙酰胆碱受体抗体的重症肌无力患者，提取外周血淋巴细胞，进而分离B淋巴细胞亚群。然后通过共培养外周血T细胞和B细胞探索干扰素调节因子1在重症肌无力中的作用机制。染色质免疫沉淀实验验证了干扰素调节因子1与CD180启动子区间互作。双荧光素酶报告基因证实了干扰素调节因子1在CD180启动子上的转录活性。体外研究进一步表明，干扰素调节因子1可通过抑制CD180促进B细胞活化和T细胞分化。此外，干扰素调节因子1还可通过招募组蛋白去乙酰化酶1来抑制CD180转录。而组蛋白去乙酰化酶1也能促进B细胞活化和T细胞分化。最后体外研究表明，CD180可通过抑制Toll样受体4/丝裂原活化蛋白激酶/核因子κB通路抑制B细胞活化和T细胞分化。因此，干扰素调节因子1可通过Toll样受体4/丝裂原活化蛋白激酶/核因子κB通路招募组蛋白去乙酰化酶1阻断重症肌无力中B细胞CD180的转录，从而增强T细胞分化。此项研究不仅揭示了干扰素调节因子1在重症肌无力中的重要作用及分子机制，还为重症肌无力的诊断和治疗提供了新思路和新靶点，具有重要的科学意义和临床应用价值。


https://orcid.org/0000-0002-8377-8437 (Liqun Xu)

关键词: 自身免疫性疾病, B细胞, CD180, HDAC1, IRF1, MAPK, 重症肌无力, NF-κB, T细胞, Toll样受体4

Abstract: Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis. However, its function in myasthenia gravis remains unclear. Herein, we explored the function of interferon regulatory factor 1 in myasthenia gravis, with an aim to understand the underlying mechanisms. Patients with myasthenia gravis who had acetylcholine receptor antibodies were included in the study. Peripheral blood lymphocytes were extracted from the included patients, and B lymphocyte subsets were isolated. Next, T and B cells from peripheral blood were co-cultured to explore the interferon regulatory factor 1-related mechanisms in myasthenia gravis. Chromatin immunoprecipitation experiments confirmed an interaction between interferon regulatory factor 1 and the CD180 promoter region. Dual-luciferase reporter gene confirmed the transcriptional activity of interferon regulatory factor 1 on CD180 promoter. In vitro results further indicated that interferon regulatory factor 1 promoted B cell activation and T cell differentiation via the inhibition of CD180. Interferon regulatory factor 1 recruited histone deacetylase 1 to inhibit CD180 transcription. Additionally, histone deacetylase 1 promoted B cell activation and T cell differentiation. Finally, in vitro experiments demonstrated that CD180 inhibited B cell activation and T cell differentiation by inhibiting the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway. Collectively, our results suggest that interferon regulatory factor 1 enhances T cell differentiation by recruiting histone deacetylase 1 to block B cell CD180 transcription in myasthenia gravis via the Toll-like receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway. Together, these findings indicate the important role of interferon regulatory factor 1 in myasthenia gravis and suggest its molecular mechanisms. They also provide new ideas and targets for diagnosing and treating myasthenia gravis, which will be both scientifically and clinically valuable. 

Key words: autoimmune condition, B cell, CD180, histone deacetylase 1, interferon regulatory factor 1, mitogen-activated protein kinase, myasthenia gravis, nuclear factor-kappa B, T cell, Toll-like receptor 4