Jia Huilin, He Xingli, Jiang Tengfei, Kong Fanzhi
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, China.
Cells. 2025 Jun 18;14(12):920. doi: 10.3390/cells14120920.
Bile acids (BAs), essential for lipid metabolism and fat-soluble vitamin absorption, also act as signaling molecules that regulate immune homeostasis. This review focuses on the roles of four key BA-activated receptors, farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (GPBAR1), liver X receptors (LXRs), and vitamin D receptor (VDR), in modulating the functions of monocytes-macrophages, and dendritic cells (DCs). The biological synthesis, transport, and metabolism of BAs were discussed and highlighted the feedback mechanisms regulating the synthesis and enterohepatic circulation of BAs. Each receptor's role in shaping immune responses is detailed, including their function in inflammation, apoptosis, phagocytosis, and pathogen clearance. FXR and GPBAR1 activation generally exhibits anti-inflammatory effects, while LXR and VDR modulate a more nuanced interplay between immune responses and lipid homeostasis. We also explored the cross-talk between BA-activated receptors and Toll-like receptors, providing a comprehensive understanding of the complex interplay between BA signaling and innate immunity. This review culminates by highlighting the therapeutic potential of targeting these receptors for the treatment of inflammatory and autoimmune diseases.
胆汁酸（BAs）对脂质代谢和脂溶性维生素吸收至关重要，还作为调节免疫稳态的信号分子发挥作用。本综述聚焦于四种关键的胆汁酸激活受体，即法尼醇X受体（FXR）、G蛋白偶联胆汁酸受体1（GPBAR1）、肝X受体（LXRs）和维生素D受体（VDR）在调节单核细胞-巨噬细胞和树突状细胞（DCs）功能中的作用。讨论了胆汁酸的生物合成、转运和代谢，并强调了调节胆汁酸合成和肠肝循环的反馈机制。详细阐述了每种受体在塑造免疫反应中的作用，包括它们在炎症、凋亡、吞噬作用和病原体清除中的功能。FXR和GPBAR1的激活通常表现出抗炎作用，而LXR和VDR则调节免疫反应与脂质稳态之间更为细微的相互作用。我们还探讨了胆汁酸激活受体与Toll样受体之间的相互作用，从而全面了解胆汁酸信号与先天免疫之间的复杂相互作用。本综述最后强调了靶向这些受体治疗炎症和自身免疫性疾病的治疗潜力。
