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

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…

• EC
  European Commission

  Awards: 675395, 330621
• H2
  Horizon 2020 Framework Programme

  Award: 675395
• MR
  Medical Research Council

  Awards: MR/N501876/1, MC_UU_12022/5