江汉大学夏亦元研究组报道了白细胞介素-33敲除促进P300/CBP相关因子介导的星形胶质细胞乙酰化释放高迁移率族蛋白B1。这一研究成果发表在2025年3月10日出版的国际学术期刊《神经科学通报》上。

高移动性组框1 （HMGB1）在细胞外释放时，在脊髓突触的发育中起关键作用，并加剧中枢神经系统内的自身免疫性疾病。在实验性自身免疫性脑脊髓炎（EAE）中，一种模拟多发性硬化的疾病，细胞外HMGB1和白细胞介素-33 （IL-33）的水平被发现呈负相关。

然而，IL-33缺乏促进EAE期间HMGB1释放的机制尚不清楚。他们的研究阐明了一种潜在的信号通路，即IL-33缺失导致星形胶质细胞核中P300/ cbp相关因子与HMGB1结合增加，上调HMGB1乙酰化并促进其从EAE小鼠脊髓星形胶质细胞核中释放。相反，IL-33的加入抵消了TNF-α-诱导的原代星形胶质细胞中HMGB1和乙酰化HMGB1水平的升高。这些发现强调了il -33相关信号通路作为EAE治疗靶点的潜力。

附：英文原文

Title: 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: Xiao, Yifan, Hao, Liyan, Cao, Xinyi, Zhang, Yibo, Xu, Qingqing, Qin, Luyao, Zhang, Yixuan, Wu, Yangxingzi, Zhou, Hongyan, Wu, Mengjuan, Pi, Mingshan, Xiong, Qi, Yang, Youhua, Gui, Yuran, Liu, Wei, Zheng, Fang, Shu, Xiji, Xia, Yiyuan

Issue&Volume: 2025-03-10

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.

DOI: 10.1007/s12264-025-01374-8

Source: https://link.springer.com/article/10.1007/s12264-025-01374-8