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在小儿RSV感染期间,ATP-P2X7R通路的激活限制了Tfh细胞区

Constanza Russo¹, Silvina Raiden², Silvia Algieri³

¹Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Facultad de Medicina, Universidad de Buenos Aires- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.

Frontiers in immunology

|July 24, 2024

概括

在RSV感染期间,Tfh细胞中ATP-P2X7R通路的激活会损害免疫反应. 这种途径失调,以高ATP和改变的P2X7R活性为标志,与严重的疾病和降低的Tfh细胞功能相关.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
细胞生物学细胞生物学

背景情况:

毛囊辅助T (Tfh) 细胞对于有效的B细胞反应和抗体产生至关重要.
纯能受体P2X7 (P2X7R) 在调节Tfh细胞活性方面发挥作用.
在呼吸道同胞病毒 (RSV) 感染期间,在循环的Tfh (cTfh) 细胞中研究ATP-P2X7R轴是了解免疫失调的关键.

研究的目的:

调查ATP-P2X7R轴在儿童RSV感染期间在循环Tfh细胞中的作用.
确定ATP-P2X7R通路失调与RSV疾病严重程度之间的关联.
探索ATP-P2X7R激活对cTfh细胞功能的影响,包括增殖,亡和IL-21产生.

主要方法:

分析了两个队列:中度 (n=30) 和重度 (n=21) RSV 感染的儿童和健康的对照组 (n=23).
使用ELISA对抗PreF IgG抗体,IL-21和可溶性P2X7R (sP2X7R) 的量化.
通过光度测量测量ATP水平,并通过流细胞测量评估cTfh细胞频率,P2X7R表达和血细胞.
在体外评估cTfh细胞亡,增殖和IL-21产生的刺激与Bz-ATP和/或P2X7R抗剂 (KN-62).

主要成果:

与中度病例相比,严重的RSV感染与较低的中和抗PreF IgG抗体标位,降低的cTfh细胞频率和降低的血IL-21水平有关.
在RSV感染期间观察到血和鼻吸附物 (NPA) 中ATP水平升高,cTfh细胞上P2X7R表达增加,RSV感染期间观察到sP2X7R减少,特别是在严重病例中.
暴露于ATP影响了cTfh细胞的增殖和IL-21的产生,同时增加了细胞亡,而P2X7R抗剂KN-62减轻了这些影响. 疾病的严重程度与ATP水平呈正相关,与cTfh频率呈反相关.

结论:

在RSV感染期间cTfh细胞中ATP-P2X7R通路的激活有助于免疫功能障碍.
这种途径失调,以增加ATP和P2X7R活性为特征,促进cTfh细胞死亡并限制它们的区间.
这些发现表明,准ATP-P2X7R通路可能是改善严重RSV疾病的治疗策略.

关键词:

这就是ATPATPATP ATP.这就是为什么RSV RSV.一个 Tfh 细胞.抗体是对抗体的重要组成部分.孩子们的孩子们的孩子们的孩子们.

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