Panpan Jiang, Yukai Jing, Siyu Zhao, Caini Lan, Lu Yang, Xin Dai, Li Luo, Shaozhe Cai, Yingzi Zhu, Heather Miller, Juan Lai, Xin Zhang, Xiaochao Zhao, Yonggui Wu, Jingzhi Yang, Wen Zhang, Fei Guan, Bo Zhong, Hisanori Umehara, Jiahui Lei, Lingli Dong, Chaohong Liu
IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1β inflammatory axis...
March 23, 2024: Nature Communications