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Publication : Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR.

First Author  Zemmour D Year  2018
Journal  Nat Immunol Volume  19
Issue  3 Pages  291-301
PubMed ID  29434354 Mgi Jnum  J:282414
Mgi Id  MGI:6380849 Doi  10.1038/s41590-018-0051-0
Citation  Zemmour D, et al. (2018) Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR. Nat Immunol 19(3):291-301
abstractText  CD4(+) T regulatory cells (Treg) are central to immune homeostasis, their phenotypic heterogeneity reflecting the diverse environments and target cells that they regulate. To understand this heterogeneity, we combined single-cell RNA-seq, activation reporter and T cell receptor (TCR) analysis to profile thousands of Treg or conventional CD4(+)FoxP3(-) T cells (Tconv) from mouse lymphoid organs and human blood. Treg and Tconv pools showed areas of overlap, as resting 'furtive' Tregs with overall similarity to Tconvs or as a convergence of activated states. All Tregs expressed a small core of FoxP3-dependent transcripts, onto which additional programs were added less uniformly. Among suppressive functions, Il2ra and Ctla4 were quasiconstant, inhibitory cytokines being more sparsely distributed. TCR signal intensity did not affect resting/activated Treg proportions but molded activated Treg programs. The main lines of Treg heterogeneity in mice were strikingly conserved in human blood. These results reveal unexpected TCR-shaped states of activation, providing a framework to synthesize previous observations of Treg heterogeneity.
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