Zhang Qi, Liao Jinfeng, Liu Zheng, Song Siyuan, Tian Limin, Wang Yi
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, China.
Front Immunol. 2025 Apr 30;16:1565158. doi: 10.3389/fimmu.2025.1565158. eCollection 2025.
Regulatory B cells (Bregs) are pivotal modulators of immune tolerance, suppressing inflammation through cytokine secretion and cellular interactions. Their role is particularly significant in inflammatory diseases such as type 1 and type 2 diabetes mellitus (T1DM and T2DM), where immune dysregulation contributes to disease progression. In T1DM, Bregs mitigate β-cell autoimmunity via IL-10 production and FOXP3-mediated pathways, but genetic mutations and dysfunctions in these mechanisms exacerbate autoimmunity. In T2DM, chronic inflammation and metabolic stress impair Breg numbers and function, further fueling insulin resistance. While Bregs play a central role in T1DM by directly preventing β-cell destruction, their role in T2DM is more supportive, modulating inflammation in metabolically stressed tissues. Emerging therapeutic strategies aim to enhance Breg function through IL-10 induction, ex vivo expansion, or targeting Breg-specific pathways using gene-editing and small molecules. Future research should explore Breg heterogeneity, novel markers, and personalized therapies to unlock their full potential. Understanding and leveraging the immune tolerance role of Bregs may offer transformative strategies to inhibit inflammatory diseases like diabetes mellitus.
调节性B细胞（Bregs）是免疫耐受的关键调节因子，通过细胞因子分泌和细胞间相互作用抑制炎症。它们在1型和2型糖尿病（T1DM和T2DM）等炎症性疾病中的作用尤为重要，在这些疾病中免疫失调会促进疾病进展。在T1DM中，Bregs通过产生IL-10和FOXP3介导的途径减轻β细胞自身免疫，但这些机制中的基因突变和功能障碍会加剧自身免疫。在T2DM中，慢性炎症和代谢应激会损害Bregs的数量和功能，进一步加剧胰岛素抵抗。虽然Bregs通过直接防止β细胞破坏在T1DM中发挥核心作用，但其在T2DM中的作用更具支持性，可调节代谢应激组织中的炎症。新兴的治疗策略旨在通过诱导IL-10、体外扩增或使用基因编辑和小分子靶向Breg特异性途径来增强Breg功能。未来的研究应探索Breg的异质性、新型标志物和个性化疗法，以充分发挥其潜力。了解并利用Bregs的免疫耐受作用可能会为抑制糖尿病等炎症性疾病提供变革性策略。
