Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation

作者：Ricardo J. Miragaia, Tomás Gomes, Agnieszka Chomka, Laura Jardine, Angela Riedel, Ahmed N. Hegazy, Natasha Whibley, A. Tucci, Xi Chen, Ida Lindeman, Guy Emerton, Thomas Krausgruber, Jacqueline D. Shields, Muzlifah Haniffa, Fiona Powrie, Sarah A. Teichmann · 发表于：Immunity · 年份：2019 · DOI：10.1016/j.immuni.2019.01.001 · 被引用次数：542 · 研究领域：T-cell and B-cell Immunology、Single-cell and spatial transcriptomics、Immune Cell Function and Interaction

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.