Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.

Yifan XIAO; Liyan HAO; Xinyi CAO; Yibo ZHANG; Qingqing XU; Luyao QIN; Yixuan ZHANG; Yangxingzi WU; Hongyan ZHOU; Mengjuan WU; Mingshan PI; Qi XIONG; Youhua YANG; Yuran GUI; Wei LIU; Fang ZHENG; Xiji SHU; Yiyuan XIA

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Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.

Author: Yifan XIAO ¹ ; Liyan HAO ¹ ; Xinyi CAO ¹ ; Yibo ZHANG ¹ ; Qingqing XU ¹ ; Luyao QIN ¹ ; Yixuan ZHANG ¹ ; Yangxingzi WU ¹ ; Hongyan ZHOU ¹ ; Mengjuan WU ¹ ; Mingshan PI ¹ ; Qi XIONG ¹ ; Youhua YANG ¹ ; Yuran GUI ¹ ; Wei LIU ¹ ; Fang ZHENG ² ; Xiji SHU ³ ; Yiyuan XIA ⁴
Author Information

1. Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan, 430056, Hubei, China.
2. Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
3. Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan, 430056, Hubei, China. xijishu@jhun.edu.cn.
4. Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan, 430056, Hubei, China. xyy@jhun.edu.cn.
Publication Type:Journal Article
Keywords: Astrocytes; Experimental autoimmune encephalomyelitis; High mobility group box 1; Interleukin-33; P300/CBP-associated factor
MeSH: Animals; Encephalomyelitis, Autoimmune, Experimental/metabolism*; Astrocytes/metabolism*; Interleukin-33/metabolism*; HMGB1 Protein/metabolism*; Acetylation; Mice, Knockout; Mice, Inbred C57BL; p300-CBP Transcription Factors/metabolism*; Mice; Spinal Cord/metabolism*; Cells, Cultured; Female; Signal Transduction
From: Neuroscience Bulletin 2025;41(7):1181-1197
CountryChina
Language:English
Abstract: High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.