由CD64+炎性2型树突细胞激活自然杀手细胞的MICa/b-依赖激活有助于自身免疫
Ildefonso Sánchez-Cerrillo1, Diego Calzada-Fraile1,2, Ana Triguero-Martínez3
1Immunology Unit, Hospital Universitario La Princesa, Medicine Department, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria-Princesa IIS-IP, Madrid, Spain.
The EMBO journal
|November 2, 2023
概括
自然杀伤细胞 (NK) 和树突细胞 (DC) 在原发性Sjögren综合征 (pSS) 中起着关键作用. 这项研究揭示了这些免疫细胞如何相互作用驱动pSS病理,识别潜在的新治疗点.
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
- 具有天生的免疫力.
背景情况:
- 主要Sjögren综合征 (pSS) 是一种自身免疫性疾病,主要是由I型和II型干扰素 (IFN) 驱动的.
- 天生免疫细胞,如自然杀手细胞 (NK) 和树突细胞 (DC) 在pSS病变发生过程中的作用尚未完全理解.
研究的目的:
- 研究NK细胞和常规树突细胞亚型2 (cDC2) 在原发性Sjögren综合征中的贡献和相互作用.
- 在这些细胞相互作用中识别潜在的治疗点.
主要方法:
- 流细胞测量用于识别和量化pSS患者的特定NK细胞 (CD16+CD56hi) 和cDC2 (CD64+) 子集.
- 活体共培养试验评估了pSS cDC2和NK细胞之间的相互作用.
- 对干扰素 (IFN) 信号的分析及其对cDC2上的NKG2D连接体表达的影响2.
- 在体内研究使用多I:C注射来模仿炎症状况.
主要成果:
- 在pSS个体中发现了细胞毒性CD16+CD56hiNK细胞和表达NKG2D连接体 (MICa/b) 的炎症性CD64+cDC2的比例增加.
- 来自pSS的cDC2有效地激活了NK细胞,并且位于唾液腺中的NK细胞附近.
- IFN通路激活 (RIG-I/DDX60,IFN I受体) 与cDC2.2上的NKG2D连接体表达相关.
- 在poly I:C后的唾液腺中观察到CD64hi RAE-1+ cDC2和NKG2D+ NK细胞的升高.
结论:
- NK细胞和cDC2细胞在pSS病理学中起着重要作用.
- 通过IFN信号调节的cDC2和NK细胞之间的相互作用有助于pSS的发病.
- 准cDC2-NK细胞轴为pss提供了一个潜在的治疗策略.
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