在减轻1型糖尿病进展方面,TIGIT+ B细胞的保护作用
Yiman Peng1, Jingyue Li1, Ying Deng2
1National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
在1型糖尿病 (T1D) 中,TIGIT+B细胞减少,抑制T细胞炎症. 针对这些细胞的疗法有望预防T1D发病和高血糖症.
科学领域:
- 免疫学
- 内分泌学
- 自体免疫性
背景情况:
- 1型糖尿病 (T1D) 涉及胰腺β细胞的自身免疫破坏,而T细胞是关键因素.
- 虽然T细胞参与,但B细胞也对T1D的发病有所贡献.
- TIGIT (具有免疫球蛋白和ITIM域的T细胞免疫受体) 是一种抑制性免疫检查点,对免疫平衡至关重要,也是自身免疫性疾病的点.
研究的目的:
- 研究TIGIT表达B细胞 (TIGIT+B细胞) 在1型糖尿病 (T1D) 进展中的作用.
- 描述T1D中TIGIT+B细胞的功能,代谢和调节性质.
- 评估针对TIGIT+B细胞进行T1D免疫治疗的治疗潜力.
主要方法:
- 用流细胞测量分析TIGIT+B细胞频率和特征在T1D患者和非肥胖的糖尿病小鼠 (NOD).
- 在体外共同培养实验中评估了TIGIT+ B细胞对T细胞的调节机制.
- 在体内干预研究中,NOD小鼠接受了TIGIT免疫球蛋白治疗和TIGIT+B细胞的采用转移.
主要成果:
- 在T1D中,TIGIT+B细胞的发生频率降低,与疾病进展有负相关性.
- TIGIT+B细胞表现出减少的共刺激,激活,增殖,促炎细胞因子的产生和葡萄糖代谢,同时增加了抗炎细胞因子的产生.
- 在体外,TIGIT+ B细胞抑制了T细胞的炎症分化和致病功能.
- 在NOD小鼠中,TIGIT- 免疫球蛋白和TIGIT+ B细胞的采用转移预防了T1D发病和高血糖症.
结论:
- 在T1D中,TIGIT+ B细胞具有抑制自身免疫反应的调节功能.
- 向TIGIT+B细胞代表了一种潜在的新型免疫治疗策略.
- 这项研究为开发TIGIT+ B细胞治疗T1D提供了基础.
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