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

Published version
Peer-reviewed

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Authors

Miragaia, Ricardo J 
Gomes, Tomás 
Chomka, Agnieszka 
Jardine, Laura 
Riedel, Angela 

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

Adaptation, Physiological, Animals, Cell Line, Tumor, Cell Movement, Colon, Humans, Immunologic Memory, Lymphoid Tissue, Mice, Transgenic, Neoplasms, Experimental, Single-Cell Analysis, Skin, Spleen, T-Lymphocytes, Regulatory, Transcriptome

Journal Title

Immunity

Conference Name

Journal ISSN

1074-7613
1097-4180

Volume Title

50

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_UU_12022/5)
MRC (unknown)
MRC (MR/N501876/1)
MRC (MR/N501876/1)