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Immunity. 2019 Jan 23. pii: S1074-7613(19)30001-9. doi: 10.1016/j.immuni.2019.01.001. [Epub ahead of print]

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

Author information

1
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Centre of Biological Engineering, University of Minho, Braga, Portugal.
2
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
3
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Experimental Medicine Division Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
4
Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK.
5
MRC Cancer Unit, University of Cambridge, Cambridge, UK.
6
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
7
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway.
8
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Theory of Condensed Matter, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK. Electronic address: st9@sanger.ac.uk.

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.

PMID:
30737144
DOI:
10.1016/j.immuni.2019.01.001
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