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

Abstract

Highlights d Single-cell RNA-seq reveals differential tissue-specific adaptation of Vg6 + T cells d Skin Vg6 + T cells show an activated IL-17-and amphiregulinproducing effector phenotype d Expression of Bcl2a1 family proteins protect activated skin Vg6 + T cells from apoptosis d Skin Vg6 + and Vg4 + T cells can be distinguished by Scart1 versus Scart2 expression

Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

“…In mouse skin, a self-renewing population of dermal γδ T cells was identified as the major source of IL-17 in steady state (Gray et al, 2011;Sumaria et al, 2011). These IL-17-producing γδ T cells (γδ17 cells) in the dermis are chronically activated by local signals and fairly tissue-resident (Laidlaw et al, 2019;Tan et al, 2019). In human skin, the contribution of γδ17 cells and other innate lymphocytes to steady state IL-17 production is currently less clear (Brüggen et al, 2016).…”

A fetal wave of human type-3 γδ T cells with restricted TCR diversity persists into adulthood

“…GM_A included genes such as LEF1 and TCF7 that are key regulators of naïve T cells 22,23 as well as known regulatory TFs of murine immature γδ T cells (e.g. SOX4) 13,24 (Fig. 2a).…”

“…The module GM_G indicated acute T cell activation in c2 and c7. Of note, the type-3 immunity gene module GM_D, characterized by gene signatures connected to interleukin-17 (IL-17) producing T cells 13,[26][27][28] , was exclusively enriched within c8, which contained neonatal as well as adult γδ T cells ( Fig. 2 and Supplementary Fig.…”

“…In mice, distinct waves of effector γδ T cells with restricted TCR diversity develop sequentially in the fetal thymus 11 . In particular, IL-17-producing effector γδ T (γδT17) cells are exclusively generated before birth and persist throughout the entire life as self-renewing, tissue-resident T cells in a diverse range of tissues 12,13 . There are parallels in humans, as Vγ9Vδ2 + T cells with restricted TCR diversity are preferentially generated before birth, expand postnatally and persist into adulthood [14][15][16][17] .…”

Dendritic cells require TMEM176A/B ion channels for optimal MHC II antigen presentation to naive CD4+ T cells

“…to as type 3 (or type 17) immune cells, producing the prototypical cytokines IL-17 and IL-22 and including Th17 CD4 + T cells, gdT17 cells, group 3 innate lymphoid cells (ILC3s) and NKT17 cells 6,[11][12][13][14] . Moreover, the Littman group included Tmem176a/b in the restricted group of 11 genes whose expression is directly dependent on RORγt in Th17 cells 15 .…”