Inhibition of EED-mediated histone methylation alleviates neuroinflammation by suppressing WNT-mediated dendritic cell migration.

IF 9.3 1区医学 Q1 IMMUNOLOGY

Journal of Neuroinflammation Pub Date : 2025-04-01 DOI:10.1186/s12974-025-03429-z

Wenxiang Hong, Hongbo Ma, Zhibin Li, Yiwen Du, Wenjing Xia, Han Yin, Han Huang, Zebing Sun, Renhua Gai, Lexian Tong, Hong Zhu, Jincheng Wang, Bo Yang, Qiaojun He, Qinjie Weng, Jiajia Wang

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引用次数: 0

Abstract

The epigenetic modification of histone H3 lysine 27 trimethylation (H3K27me3) by the embryonic ectoderm development (EED) protein is closely associated with the regulation of transcriptional programs and is implicated in autoimmune diseases. However, the efficacy of targeting H3K27me3 for the treatment of neuroinflammation remains unclear. In this study, we demonstrate that systemic administration of an EED inhibitor diminishes the inflammatory response mediated by dendritic cells (DCs), thereby alleviating experimental autoimmune encephalitis (EAE), a representative mouse model of autoimmune diseases in the central nervous system (CNS). Our findings indicate that EED inhibitors suppress DC migration by upregulating genes in the WNT signaling pathway that are epigenetically marked by H3K27me3. Conversely, inhibiting the WNT pathway partially reverses the impaired DC migration caused by EED inhibitors. Additionally, the genetic deletion of Eed inhibits DC migration and effectively mitigates autoimmune symptoms and inflammatory infiltration into the CNS in EAE. These results highlight EED as a critical regulator of DC migration and suggest its potential as a therapeutic target for autoimmune disorders.

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来源期刊

Journal of Neuroinflammation 医学-神经科学

CiteScore

15.90

自引率

3.20%

发文量

276

审稿时长

1 months

期刊介绍： The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes. Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems. The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.