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

作者：Likai Tan, Inga Sandrock, Ivan Odak, Yuval Aizenbud, Anneke Wilharm, Joana Barros‐Martins, Yaara Tabib, Alina Borchers, Tiago Amado, Lahiru Gangoda, Marco J. Herold, Marc Schmidt‐Supprian, Jan Kisielow, Bruno Silva‐Santos, Christian Koenecke, Avi‐Hai Hovav, Christian F. Krebs, Immo Prinz, Sarina Ravens · 发表于：Cell Reports · 年份：2019 · DOI：10.1016/j.celrep.2019.05.064 · 被引用次数：133 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、IL-33, ST2, and ILC Pathways

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.