Spleen fibroblastic reticular cell-derived acetylcholine promotes lipid metabolism to drive autoreactive B cell responses.-猫眼课题宝

DOI：

10.1016/j.cmet.2023.03.010

发表时间：

2023-03

期刊：

Cell metabolism

影响因子：

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Qin Zeng;Shuyi Wang;Mengyuan Li;Shuang Wang;Chaohuan Guo;Xinyuan Ruan;R. Watanabe;Yimei Lai;Yuefang Huang;Xiaoyu Yin;Chuanzhao Zhang;Binfeng Chen;N. Yang;Hui Zhang

自身反应性 B 细胞反应对于系统性红斑狼疮 (SLE) 的发展至关重要。众所周知，成纤维网状细胞（FRC）可以构建淋巴室并调节免疫功能。在这里，我们确定脾脏 FRC 衍生的乙酰胆碱 (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，抑制脂肪酸氧化会导致狼疮小鼠自身反应性 B 细胞反应减少并改善疾病。 B 细胞中 CD36 的消除会损害自身免疫诱导过程中自身反应性 B 细胞的脂质摄取和分化。从机制上讲，脾脏 FRC 衍生的 ACh 通过 CD36 促进脂质流入和自身反应性 B 细胞的生成。总之，我们的数据揭示了脾 FRC 在脂质代谢和 B 细胞分化中的新功能，使脾 FRC 衍生的 ACh 在促进 SLE 自身反应性 B 细胞中发挥关键作用。

Autoreactive B cell responses are essential for the development of systemic lupus erythematosus (SLE). Fibroblastic reticular cells (FRCs) are known to construct lymphoid compartments 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 phosphorylation in B cells. Accordingly, the inhibition of fatty acid oxidation results in reduced autoreactive B cell responses and ameliorated diseases in lupus mice. Ablation of CD36 in B cells impairs lipid uptake and differentiation of autoreactive B cells during autoimmune induction. Mechanistically, spleen FRC-derived ACh promotes lipid influx and generation of autoreactive B cells through CD36. Together, our data uncover a novel function of spleen FRCs in lipid metabolism and B cell differentiation, placing spleen FRC-derived ACh in a key position in promoting autoreactive B cells in SLE.

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

文献摘要

相似文献