Shao Yongqi, Mei Yang, Tan Yixin, Yang Ming, Wu Haijing
Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
Cell Biosci. 2025 Apr 30;15(1):57. doi: 10.1186/s13578-025-01398-7.
Autoimmune diseases are characterized by a dysfunction of the immune system. Disruptions in the balance of B-cell dynamics and the increase in auto-antibody levels are pivotal in the triggering of several autoimmune disorders. All of this is inextricably linked to the differentiation, development, migration, and functional regulation of B cells in the human immune response. G protein-coupled receptors (GPCR) are recognized as crucial targets in drug development and play pivotal roles in both B cell differentiation and the underlying mechanisms of autoimmune diseases. However, there has been an inadequate comprehension of how GPCR intricately modulate B cell development and impact the pathogenesis of autoimmune diseases. Ligands and functions of GPCR-chemokine receptors including CXCR3, CXCR4, CXCR5 and CCR7, lipid receptors including S1PR1-5, cannabinoid receptor CB2 as well as orphan GPCR including GPR132, GPR183, GPR174, and P2RY8 in B cell differentiation and development, will be elaborated in this review. The roles these GPCR play in mediating B cells in several autoimmune diseases will also be discussed. The elucidation of the multifaceted mechanisms controlled by GPCR not only enriches our comprehension of immune responses but also provides a promising avenue for therapeutic interventions in the domain of autoimmune disorders.
自身免疫性疾病的特征是免疫系统功能失调。B细胞动态平衡的破坏和自身抗体水平的升高在多种自身免疫性疾病的触发中起关键作用。所有这些都与人类免疫反应中B细胞的分化、发育、迁移和功能调节有着千丝万缕的联系。G蛋白偶联受体（GPCR）被认为是药物开发中的关键靶点，在B细胞分化和自身免疫性疾病的潜在机制中都起着关键作用。然而，对于GPCR如何复杂地调节B细胞发育以及影响自身免疫性疾病的发病机制，人们的理解还不够充分。本文将阐述GPCR-趋化因子受体（包括CXCR3、CXCR4、CXCR5和CCR7）、脂质受体（包括S1PR1-5）、大麻素受体CB2以及孤儿GPCR（包括GPR132、GPR183、GPR174和P2RY8）在B细胞分化和发育中的配体及功能。还将讨论这些GPCR在几种自身免疫性疾病中介导B细胞的作用。对GPCR所控制的多方面机制的阐明，不仅丰富了我们对免疫反应的理解，也为自身免疫性疾病领域的治疗干预提供了一条有前景的途径。
