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<p>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.</p><p></p>

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WASH regulates B cell signaling, metabolism and function through STAT1

  • 期刊论文

  • 发表日期：

    2025年12月23日

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  • Panpan Jiang,
  • Caini Lan,
  • Siyu Zhao,
  • Xin Zhang,
  • Juan Lai,
  • Yukai Jing,
  • Xin Dai,
  • Li Luo,
  • Na Li,
  • Qiuyue Chen,
  • Qian Liu,
  • Xiaoyu Li,
  • Shuhan Chen,
  • Zhangfan Wu,
  • Junyang Zhou,
  • Heather Miller,
  • Ruyuan Wang,
  • Fei Guan,
  • Lu Yang,
  • Weibing Kuang,
  • Xingrong Du,
  • Pengyan Xia,
  • Zhen-Li Huang,
  • Jun He,
  • Zheng Liu,
  • Zusen Fan,
  • Jiahui Lei,
  • Chaohong Liu

摘要

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.