Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells

Neutrophilic asthma is associated with disease severity and corticosteroid insensitivity. Novel therapies are required to manage this life-threatening asthma phenotype. Programmed cell death protein-1 (PD-1) is a key homeostatic modulator of the immune response for T cell effector functions. Our study was conducted to assess the therapeutic potential of a novel human PD-1 agonist in a humanized mouse model in which the PD-1 extracellular domain is entirely humanized. Using single-cell RNA sequencing, we demonstrated that PD-1 agonist treatment alleviates lung inflammation via the reprogramming of pulmonary effector T cells. Overall design: mRNA profiles of lung CD45+ cells from isotype- and PD-1 agonist treated humanized PD-1 mice were generated by deep sequencing. Three samples from each group were mixed using the cell hashing technique (?50,000 cells/group).

中性粒细胞性哮喘与疾病严重程度及糖皮质激素耐药性密切相关，针对这一危及生命的哮喘表型，亟需开发新型治疗策略。程序性死亡蛋白-1（Programmed cell death protein-1, PD-1）是调控T细胞效应功能的免疫应答关键稳态调节因子。本研究旨在评估一种新型人源PD-1激动剂在PD-1胞外结构域完全人源化的人源化小鼠模型中的治疗潜力。采用单细胞RNA测序技术，我们证实PD-1激动剂可通过重编程肺部效应T细胞缓解肺部炎症。总体实验设计：通过深度测序获取同型对照处理与PD-1激动剂处理的人源化PD-1小鼠肺部CD45+细胞的mRNA表达谱。每组各3份样本通过细胞哈希技术进行混合，每组样本约含50,000个细胞。