Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation.
Published version
Peer-reviewed
Repository URI
Repository DOI
Type
Change log
Authors
Abstract
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.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
1097-4180
Volume Title
Publisher
Publisher DOI
Sponsorship
MRC (unknown)
MRC (MR/N501876/1)
MRC (MR/N501876/1)