Analysis of lung transcriptomic changes following inhibition of LTβR-signalling in cigarette smoke exposed mice. Analysis of lung transcriptomic changes following inhibition of LTβR-signalling in cigarette smoke exposed mice

How LTβR-signalling drives chronic tissue damage particularly in the lung, which mechanisms regulate this process, and whether LTβR-blockade might be of therapeutic value has remained unclear. To study the mechanisms underlying LTβR-inhibition, a transcriptional analysis was performed on lung tissue from B6 mice exposed to cigarette smoke for 6 months and treated therapeutically with LTβR-Ig from 4 to 6 months compared to mice exposed to cigarette smoke for 6 months and treated with control Ig from 4 to 6 months and filtered air control. Single-cell RNA-Seq identified 24 distinct cell populations across >20,000 cells in lungs with distinct changes occurring upon cigarette smoke exposure and LTβR-Ig treatment. Overall design: Single-cell transcriptomics experiment after cigarette smoke exposure and drug treatment.

淋巴毒素β受体信号通路（LTβR-signalling）如何介导慢性组织损伤（尤其在肺部）、哪些机制调控该过程，以及淋巴毒素β受体阻断（LTβR-blockade）是否具有治疗价值，此前一直尚不明确。为探究LTβR抑制的潜在分子机制，研究人员对三组小鼠的肺组织开展转录组分析：分别为暴露于香烟烟雾6个月、并于第4至6个月接受LTβR-免疫球蛋白（LTβR-Ig）治疗的小鼠；暴露于香烟烟雾6个月、并于第4至6个月接受对照免疫球蛋白（control Ig）治疗的小鼠；以及暴露于过滤空气的对照组小鼠。单细胞RNA测序（single-cell RNA-Seq）在超过20000个肺细胞中鉴定出24种独立细胞群，且香烟烟雾暴露与LTβR-Ig治疗均可引发细胞群的显著改变。实验整体设计：香烟烟雾暴露联合药物处理后的单细胞转录组学实验。