GABA signaling enforces intestinal germinal center B cell differentiation

作者：Yuexia Liao, Lijuan Fan, Peng Bin, Congrui Zhu, Qingyi Chen, Yepeng Cai, Jielin Duan, Qian Cai, Wei Han, Shizhen Ding, Xiangyu Hu, Yiran Zhang, Yulong Yin, Wenkai Ren · 发表于：Proceedings of the National Academy of Sciences · 年份：2022 · DOI：10.1073/pnas.2215921119 · 被引用次数：33 · 研究领域：Immune Cell Function and Interaction、Gastrointestinal motility and disorders、T-cell and B-cell Immunology

B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.