人体在体外诱导的IL-17A+ CD8+ T细胞对突纤维细胞产生促炎作用
Elizabeth H Gray1, Ushani Srenathan1, Lucy E Durham1
1Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology & Microbial Sciences, King's College London, London, UK.
人类IL-17A+ CD8+ T细胞 (Tc17细胞) 在体外成功扩展,揭示了它们独特的17型特征和促炎功能. 这些发现表明免疫介导炎症疾病的潜在治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 炎症研究 炎症研究
背景情况:
- 产生IL-17A的CD8+T细胞 (Tc17细胞) 与免疫介导的炎症性疾病有关.
- 由于人体Tc17细胞的数量有限,人类Tc17细胞的确切生物学作用仍然不完全理解.
研究的目的:
- 描述人类IL-17A+ CD8+ T细胞的生物功能.
- 为人类Tc17细胞建立一个体外扩展协议.
主要方法:
- 从健康的供体PBMC中扩展IL-17A+ CD8+ T细胞,使用与IL-1β和IL-23的体外极化协议.
- 通过转录概况,表面标记分析 (CCR6,CD161) 和细胞因子生产 (IL-17A,IL-17F,IL-22,IFNγ,TNFα,GM-CSF) 来表征扩展细胞.
- 通过与牛皮关节炎患者的突纤维细胞共同培养排序的Tc17细胞并测量炎症性细胞因子诱导,评估功能能力.
主要成果:
- 在体外,IL-1β和IL-23显著增加了IL-17A+ CD8+ T细胞的频率.
- 在体外生成的TC17细胞表现出17型的转录特征和多功能细胞因子的产生.
- 扩张的Tc17细胞,包括MAIT细胞,诱导了突纤维细胞的益炎性IL-6和IL-8产生,这种产生被抗TNFα和抗IL-17A抗体抑制.
结论:
- 在体外生成的人类IL-17A+ CD8+ T细胞具有生物学功能.
- 现有的免疫疗法可以向TC17细胞的促炎活性,提供潜在的治疗策略.
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