通过深度测序来识别与Sjögren病相关的T细胞受体动机
Ananth Aditya Jupudi1,2, Michelle L Joachims1,3, Christina Lawrence1
1Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
JCI insight
|December 22, 2025
概括
在Sjögren病 (SjD) 中的T细胞受体分析显示患者的血液T细胞谱系受到限制. 扩大的唾液腺T细胞与血液共享独特的受体,与疾病严重程度相关,并识别潜在的Ro60自身抗原.
科学领域:
- 免疫学 免疫学 免疫学
- 自免疫性疾病 自免疫性疾病
- 分子生物学分子生物学
背景情况:
- CD4+ T细胞是Sjögren病 (SjD) 唾液腺炎症的关键参与者.
- 了解SjD中的T细胞受体 (TCR) 信息库对于识别疾病特异性抗原和致病机制至关重要.
研究的目的:
- 描述SjGren病患者和健康对照人群 (HCs) 之间的TCR曲目差异.
- 为了研究唾液腺 (SG) 和外周血液 (PB) 之间的关系,SjD中的TCR剧目.
- 在SjD中识别由致病性T细胞克隆识别的特定抗原.
主要方法:
- 从SjD病例和HC的PB中对CD4+CD45RA-T细胞进行深度测序.
- 从SjD病例的唇部SG活检中CD4+T细胞的单细胞TCR测序.
- 分析TCR曲目多样性,克隆型扩展和图案识别.
主要成果:
- 在SjD患者中,克隆扩展的SG CD4+ T细胞与PB共享TCR CDR3序列.
- SjD病例表现出受限的PB TCR剧目,多样性减少.
- 在SG和PB之间共享的SjD相关的TCR动机,与减少的唾液流相关.
- 发现了两个Ro60表位,触发了SG T细胞克隆的HLA受限免疫反应.
结论:
- 在SjD中全面的TCR曲目表征提供了对疾病发病的洞察力.
- 已识别的共享TCR序列和特定的自身抗原 (Ro60表位) 提供了潜在的治疗点.
- 将T细胞对疾病特征的反应与唾液流量减少等特征联系起来,突出了它们的病原性作用.
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