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

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.