小柯机器人

复旦大学林玉丽、杨旭光、尹波和陈杰研究组合作发现低密度脂蛋白受体 (VLDLR)增强胰腺星状细胞脂质代谢，并促进胰腺纤维化。2022年6月22日出版的《免疫》发表了这项成果。

他们研究了脂蛋白代谢物激活胰腺星状细胞（PSC）的发生和机制以及随后对2型免疫反应的调节，以及纤维化侵袭性的驱动力在慢性胰腺炎（CP）。单细胞 RNA 测序揭示了 PSC 的异质性，并确定了以较高脂质代谢为特征的VLDLR+ PSC。VLDLR 促进细胞内脂质积累，随后白细胞介素 33 (IL-33) 在 PSCs 中表达和释放。PSC 来源的 IL-33 强烈诱导胰腺第 2 组先天性淋巴细胞 (ILC2s) 引发伴随激活的 2 型免疫反应PSCs，最终导致胰腺炎期间的纤维化。

他们的研究结果表明，PSC 中 VLDLR 增强的脂蛋白代谢促进了胰腺纤维化，并突出了 IL-33 在这种促纤维化级联反应中的主导作用。

据悉，脂蛋白紊乱是CP的共同特征；然而，脂蛋白紊乱与胰腺纤维化环境之间的关系尚不清楚。

附：英文原文

Title: Very-low-density lipoprotein receptor-enhanced lipid metabolism in pancreatic stellate cells promotes pancreatic fibrosis

Author: Xuguang Yang, Jie Chen, Jun Wang, Shuai Ma, Wenxue Feng, Zhihao Wu, Yangyang Guo, Hong Zhou, Wenli Mi, Wei Chen, Bo Yin, Yuli Lin

Issue&Volume: 2022-06-22

Abstract: Lipoprotein disorder is a common feature of chronic pancreatitis (CP); however, therelationship between lipoprotein disorder and pancreatic fibrotic environment is unclear.Here, we investigated the occurrence and mechanism of pancreatic stellate cell (PSC)activation by lipoprotein metabolites and the subsequent regulation of type 2 immuneresponses, as well as the driving force of fibrotic aggressiveness in CP. Single-cellRNA sequencing revealed the heterogeneity of PSCs and identified very-low-densitylipoprotein receptor (VLDLR)+ PSCs that were characterized by a higher lipid metabolism. VLDLR promoted intracellularlipid accumulation, followed by interleukin-33 (IL-33) expression and release in PSCs.PSC-derived IL-33 strongly induced pancreatic group 2 innate lymphoid cells (ILC2s)to trigger a type 2 immune response accompanied by the activation of PSCs, eventuallyleading to fibrosis during pancreatitis. Our findings indicate that VLDLR-enhancedlipoprotein metabolism in PSCs promotes pancreatic fibrosis and highlight a dominantrole of IL-33 in this pro-fibrotic cascade.

DOI: 10.1016/j.immuni.2022.06.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00239-4

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