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Cell Rep. 2019 Jun 18;27(12):3657-3671.e4. doi: 10.1016/j.celrep.2019.05.064.

Single-Cell Transcriptomics Identifies the Adaptation of Scart1+ Vγ6+ T Cells to Skin Residency as Activated Effector Cells.

Author information

1
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
2
Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Jerusalem 91120, Israel.
3
Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
4
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
5
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
6
Institute of Experimental Hematology, TranslaTUM, Klinikum rechts der Isar der Technischen Universität München, 81675 Munich, Germany.
7
Institute of Molecular Health Science, ETH Zuerich, 8093 Zuerich, Switzerland.
8
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
9
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: prinz.immo@mh-hannover.de.
10
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: ravens.sarina@mh-hannover.de.

Abstract

IL-17-producing γδ T cells express oligoclonal Vγ4+ and Vγ6+ TCRs, mainly develop in the prenatal thymus, and later persist as long-lived self-renewing cells in all kinds of tissues. However, their exchange between tissues and the mechanisms of their tissue-specific adaptation remain poorly understood. Here, single-cell RNA-seq profiling identifies IL-17-producing Vγ6+ T cells as a highly homogeneous Scart1+ population in contrast to their Scart2+ IL-17-producing Vγ4+ T cell counterparts. Parabiosis demonstrates that Vγ6+ T cells are fairly tissue resident in the thymus, peripheral lymph nodes, and skin. There, Scart1+ Vγ6+ T cells display tissue-specific gene expression signatures in the skin, characterized by steady-state production of the cytokines IL-17A and amphiregulin as well as by high expression of the anti-apoptotic Bcl2a1 protein family. Together, this study demonstrates how Scart1+ Vγ6+ T cells undergo tissue-specific functional adaptation to persist as effector cells in their skin habitat.

KEYWORDS:

IL-17-producing γδ T cells; Scart1; Scart2; Vγ6(+) T cells; single-cell transcriptomics; tissue-resident γδ T cells

PMID:
31216482
DOI:
10.1016/j.celrep.2019.05.064
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