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.