ARD:NLRP3炎性小体激活的Tfh细胞对于高亲和力抗体的产生、生发中心形成和自身免疫至关重要

2022-07-09 MedSci原创 MedSci原创

T滤泡辅助细胞中NLRP3炎性小体的激活是免疫反应的一个组成部分。活化的NLRP3+ T滤泡辅助细胞群对于最佳体液反应、生发中心形成和自身免疫至关重要。

目的NLRP3炎性小体调节T细胞反应。本研究检测了NLRP3炎性小体激活在对T依赖性抗原的体液反应和系统性红斑狼疮(SLE)中调节T滤泡辅助(Tfh)细胞的作用。

方法使用荧光标记的caspase-1抑制剂探针在B6MRL/lprNZM2328小鼠以及SLE 患者和健康对照中研究了Tfh细胞的NLRP3炎性体活化MCC950NLRP3的选择性抑制剂,用于研究NLRP3炎性体激活与生发中心(GC)反应、免疫反应的抗体和自身抗体产生之间的关系。

结果B6小鼠中鉴定了免疫后Tfh细胞中的NLRP3炎性小体激活。MCC950抑制对绵羊红细胞和NP-CGG(与鸡丙种球蛋白结合的4-羟基-3-硝基苯乙酰半抗原,一种T细胞依赖性抗原,会诱发产生GC)的体液反应,减少GC反应。具有淋巴细胞特异性缺失NLRP3Casp1B6小鼠表现出次优的体液反应,GC形成受损和亲和力成熟缺陷。MRL/lpr NZM2328小鼠中,抑制NLRP3激活从而抑制了NLRP3激活的Tfh细胞扩增以及减弱的狼疮样表型。具有激活的NLRP3炎性小体的Tfh细胞表现出Tfh细胞功能和分化分子的表达增加,并且具有更强的激活B细胞的能力。在SLE患者中,疾病活动与激活的NLRP3+ Tfh群体的增加呈正相关,并且该群体对治疗的反应显著减少。

结论T滤泡辅助细胞中NLRP3炎性小体的激活是免疫反应的一个组成部分。活化的NLRP3+ T滤泡辅助细胞群对于最佳体液反应、生发中心形成和自身免疫至关重要。

 

结论:Zhao Z, Xu B, Wang S, et al. Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity. Annals of the Rheumatic Diseases 2022;81:1006-1012.

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    2022-07-10 yuandd
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    2022-07-10 vera_1207

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