biostudies-literatureWang ZDFG-Deutsche ForschungsgemeinschaftGermany's Excellence Strategy, EXC 2155 RESISTDFG-funded research group FOR2799e70061https://www.ebi.ac.uk/biostudies/studies/S-EPMC12449965biostudies-literatureUnknown55(9)γδ T cells are unconventional T cells that group into different subsets based on the usage of variable γδ T cell receptor (TCR) gene segments, body location, and functionality. γδ T cells that secrete the proinflammatory cytokine interleukin 17 (IL-17) predominantly express a Vγ4⁺ or Vγ6⁺ γδ TCR. The biology and the importance of the γδ TCR of IL-17-producing γδ T cells are not well understood. Here, we investigated the IL-17 production capability of γδ T cells in mice deficient for Vγ4⁺ and Vγ6⁺ γδ TCRs using flow cytometry, TCR-seq, and single-cell transcriptomics. Our data show that Vγ1 T cells only partially compensate for the loss of IL-17⁺ Vγ4 and Vγ6 T cell subsets in lymphoid and nonlymphoid tissues. They develop pre- and postnEuropean journal of immunologyPartial Compensation of IL-17 Production by Vγ1 T Cells in the Absence of Vγ4 and Vγ6 T Cells.PMC12449965390874280RA3077/1-2Sandrock ICoffelt SBJanssen APrinz ILupo FYang TWang ZRavens SBehrens LMfalsePartial Compensation of IL-17 Production by Vγ1 T Cells in the Absence of Vγ4 and Vγ6 T Cells.γδ T cells are unconventional T cells that group into different subsets based on the usage of variable γδ T cell receptor (TCR) gene segments, body location, and functionality. γδ T cells that secrete the proinflammatory cytokine interleukin 17 (IL-17) predominantly express a Vγ4⁺ or Vγ6⁺ γδ TCR. The biology and the importance of the γδ TCR of IL-17-producing γδ T cells are not well understood. Here, we investigated the IL-17 production capability of γδ T cells in mice deficient for Vγ4⁺ and Vγ6⁺ γδ TCRs using flow cytometry, TCR-seq, and single-cell transcriptomics. Our data show that Vγ1 T cells only partially compensate for the loss of IL-17⁺ Vγ4 and Vγ6 T cell subsets in lymphoid and nonlymphoid tissues. They develop pre- and postn2025-01-01T00:00:00Z2025 Sep2026-06-03T15:16:15.352Z2026-04-29T03:09:05.341ZS-EPMC124499654097434810.1002/eji.70061