RORγt+ c-Maf+ Vγ4+ γδ T cells are generated in the adult thymus but do not reach the periphery

T cell receptor (TCR) Vγ4-expressing γδ T cells comprise interferon γ (IFNγ)- and interleukin-17 (IL-17)-producing effector subsets, with a preference for IL-17 effector fate decisions during early ontogeny. The existence of adult-thymus-derived IL-17+ T cells (γδ17) remains controversial. Here, we use a mouse model in which T cells are generated exclusively in the adult thymus and employ single-cell chromatin state analysis to study their development. We identify adult-thymus-derived Vγ4 T cells that have all the molecular programs to become IL-17 producers. However, they have reduced IL-17 production capabilities and rarely reach the periphery. Moreover, this study provides high-resolution profiles of Vγ4 T cells in the adult thymus and lymph nodes and identifies Zeb1 as a potential γδ17 cell regulator. Together, this study provides valuable insights into the developmental traits of Vγ4 T cells during adulthood and supports the idea of age-specific signals required for thymic export and/or peripheral maturation of γδ17 cells. [Display omitted] •Molecular profiling identifies developmental plasticity of Vγ4 T cells in adult thymus•A hypomorphic mutation of Zeb1 perturbs γδ17 cells•c-Maf+ RORγt+ Vγ4 T cells that can produce IL-17 are generated from adult thymic precursors•De novo-generated Vγ4+ γδ17 cells of the adult thymus do not reach the periphery The existence of postnatal-derived IL-17-producing γδ T cells remains controversial. Yang et al. identify de novo-generated Vγ4 T cells harboring molecular programs of IL-17 producers in adult thymus. However, these c-Maf+ RORγt+ Vγ4 T cells did not reach the periphery nor did they mature into CD44high effector cells.