Jiang Panpan, Lan Caini, Zhao Siyu, Zhang Xin, Lai Juan, Jing Yukai, Dai Xin, Luo Li, Li Na, Chen Qiuyue, Liu Qian, Li Xiaoyu, Chen Shuhan, Wu Zhangfan, Zhou Junyang, Miller Heather, Wang Ruyuan, Guan Fei, Yang Lu, Kuang Weibing, Du Xingrong, Xia Pengyan, Huang Zhen-Li, He Jun, Liu Zheng, Fan Zusen, Lei Jiahui, Liu Chaohong
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Death Differ. 2025 Dec 23. doi: 10.1038/s41418-025-01647-9.
Actin and actin polymerization factors regulate the immune system in a complex manner. The function in the cytoplasm has been well-established, where they are important components of the cytoskeleton, controlling cell migration, function, and vesicular transport. However, it remains poorly understood how they enter the nucleus to regulate immunological functions in B cells. Here, our study, through constructing a mouse model with specific WASH deletion in B cells, has shown that a deficiency of WASH leads to a decrease in BCR signaling and B cell metabolism, abnormal B cell differentiation, and a reduction of humoral response. Mechanistically, WASH interacts with pSTAT1 to promote the phosphorylation of STAT1, facilitating its translocation into the nucleus and regulating biological functions. Our study has unveiled the potential molecular mechanisms by which WASH influences B cell signaling, metabolism, and function through STAT1. These findings will offer potential avenues for therapeutic strategies targeting autoimmune diseases.
