中山大学Hui Zhang、Niansheng Yang和Shuyi Wang共同合作，近期取得重要工作进展。他们研究发现，脾脏成纤维网状细胞来源的乙酰胆碱促进脂质代谢以驱动自身反应性B细胞应答。相关研究成果2023年4月4日在线发表于《细胞—代谢》杂志上。

据介绍，自身反应性B细胞反应对系统性红斑狼疮（SLE）的发展至关重要。众所周知，成纤维网状细胞（FRC）可以构建淋巴区室并调节免疫功能。

研究人员确定了脾脏FRC来源的乙酰胆碱（ACh）是控制SLE自身反应性B细胞反应的关键因素。在SLE中，CD36介导的脂质摄取导致B细胞中线粒体氧化磷酸化增强。因此，对脂肪酸氧化的抑制导致狼疮小鼠自身反应性B细胞反应减少并改善疾病。在自身免疫诱导过程中，B细胞中CD36的消融会损害自身反应性B细胞的脂质摄取和分化。从机制上讲，脾脏FRC来源的ACh通过CD36促进脂质流入和自身反应性B细胞的产生。

总之，这一数据揭示了脾脏FRC在脂质代谢和B细胞分化中的新功能，使脾脏FRC来源的ACh在SLE中促进自身反应性B细胞方面处于关键地位。

附：英文原文

Title: Spleen fibroblastic reticular cell-derived acetylcholine promotes lipid metabolism to drive autoreactive B cell responses

Author: Qin Zeng, Shuyi Wang, Mengyuan Li, Shuang Wang, Chaohuan Guo, Xinyuan Ruan, Ryu Watanabe, Yimei Lai, Yuefang Huang, Xiaoyu Yin, Chuanzhao Zhang, Binfeng Chen, Niansheng Yang, Hui Zhang

Issue&Volume: 2023-04-04

Abstract: Autoreactive B cell responses are essential for the development of systemic lupuserythematosus (SLE). Fibroblastic reticular cells (FRCs) are known to construct lymphoidcompartments and regulate immune functions. Here, we identify spleen FRC-derived acetylcholine(ACh) as a key factor that controls autoreactive B cell responses in SLE. In SLE,CD36-mediated lipid uptake leads to enhanced mitochondrial oxidative phosphorylationin B cells. Accordingly, the inhibition of fatty acid oxidation results in reducedautoreactive B cell responses and ameliorated diseases in lupus mice. Ablation ofCD36 in B cells impairs lipid uptake and differentiation of autoreactive B cells duringautoimmune induction. Mechanistically, spleen FRC-derived ACh promotes lipid influxand generation of autoreactive B cells through CD36. Together, our data uncover anovel function of spleen FRCs in lipid metabolism and B cell differentiation, placingspleen FRC-derived ACh in a key position in promoting autoreactive B cells in SLE.

DOI: 10.1016/j.cmet.2023.03.010

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00088-8