当前位置: X-MOL 学术Immunity › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation
Immunity ( IF 32.4 ) Pub Date : 2019-02-05 , DOI: 10.1016/j.immuni.2019.01.001
Ricardo J Miragaia 1 , Tomás Gomes 2 , Agnieszka Chomka 3 , Laura Jardine 4 , Angela Riedel 5 , Ahmed N Hegazy 3 , Natasha Whibley 6 , Andrea Tucci 6 , Xi Chen 2 , Ida Lindeman 7 , Guy Emerton 2 , Thomas Krausgruber 3 , Jacqueline Shields 5 , Muzlifah Haniffa 4 , Fiona Powrie 3 , Sarah A Teichmann 8
Affiliation  

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation.



中文翻译:

调节性 T 细胞的单细胞转录组学揭示了组织适应的轨迹

非淋巴组织 (NLT) 拥有大量具有大量未开发表型和发育的适应性免疫细胞。我们使用单细胞 RNA-seq 来表征小鼠皮肤和结肠、它们各自的引流淋巴结 (LN) 和脾脏中的35,000 个 CD4 +调节 (Treg) 和记忆 (Tmem) T 细胞。在这些组织中,我们确定了具有不同程度的 NLT 表型的 Treg 细胞亚群。亚群伪时间排序和基因动力学在向皮肤和结肠募集方面是一致的,但 LN 中的初始 NLT 启动和 NLT 功能适应的最后阶段反映了组织特异性差异。使用体内重现预测的动力学黑色素瘤诱导模型,验证关键调节器和受体。最后,我们分析了人类血液和 NLT Treg 和 Tmem 细胞,并确定了跨哺乳动物保守组织特征。总之,我们通过结合使用计算预测和体内验证来描述 Treg 细胞异质性和 NLT 募集之间的关系。

更新日期:2019-02-05
down
wechat
bug