在早期风湿性关节炎中,共享的肺和关节T细胞谱系是由吸烟驱动的风湿性关节炎
Koen Venken1,2, Matthias Jarlborg3,2, Frederik Stevenaert4
1Faculty of Medicine and Health Sciences, Department of Internal Medicine and Pediatrics, Ghent University, Gent, Belgium koen.venken@ugent.be.
吸烟和共享表位 (SE) HLA-DRB1基因组协同增加类风湿性关节炎 (RA) 关节中的T细胞. 在RA吸烟者中,共享的T细胞克隆链接肺和关节炎症,表明自身免疫诱导.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 遗传学 遗传学 是一个
背景情况:
- 吸烟是类风湿性关节炎 (RA) 的已知危险因素,特别是在具有共享表位 (SE) HLA-DRB1等位基因的个体中.
- 关于RA患者肺部和炎症关节中的特定T细胞动态与吸烟状况的了解仍然不充分.
研究的目的:
- 为了研究肺部和炎症关节中的T细胞特征,吸烟者与不吸烟的类风湿关节炎患者对比.
- 探索吸烟,T细胞透和RA中的自身免疫之间的潜在联系.
主要方法:
- 分析了来自17名未接受过治疗的,抗素蛋白抗体阳性RA患者的支气管洗液,血液和突样本.
- 单细胞T细胞受体 (TCR) 测序和深度免疫类型定型,以分析不同组织中的T细胞谱.
主要成果:
- 与非吸烟者相比,吸烟者的突样本中观察到增加的CD4+和CD8+T细胞和扩展的T细胞克隆型,特别是在SE+个体中.
- 在RA吸烟者的肺和关节样本中发现了相同的TCR克隆类型,许多也被检测到在循环中.
- 肺关节共享的T细胞克隆型表现出受限制的TCR基因使用和在炎症的突中具有独特的效应因子概况 (4-1BB+CD57hi).
结论:
- 在遗传倾向 (MHC),吸烟和诱导自身免疫力之间存在显著的相互作用.
- 吸烟塑造T细胞受体谱,有助于T细胞透和炎症在关节的RA患者.
- 在RA吸烟者的肺和关节之间共享的T细胞特异性突显出疾病发病的潜在系统机制.
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