Genetic models reveal origin, persistence and non-redundant functions of 
IL-17-producing γδ T cells.

Sandrock, Inga; Reinhardt, Annika; Ravens, Sarina; Binz, Christoph; Wilharm, Anneke; Martins, Joana; Oberdörfer, Linda; Tan, Likai; Lienenklaus, Stefan; Zhang, Baojun; Naumann, Ronald; Zhuang, Yuan; Krueger, Andreas; Förster, Reinhold; Prinz, Immo

doi:10.1084/jem.20181439

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Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells.

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Naumann, Ronald
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Sandrock, I., Reinhardt, A., Ravens, S., Binz, C., Wilharm, A., Martins, J., et al. (2018). Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells. The Journal of experimental medicine, 215(12), 3006-3018. doi:10.1084/jem.20181439.

Cite as: https://hdl.handle.net/21.11116/0000-0003-F679-0

Abstract

γδ T cells are highly conserved in jawed vertebrates, suggesting an essential role in the immune system. However, γδ T cell-deficient Tcrd-/- mice display surprisingly mild phenotypes. We hypothesized that the lack of γδ T cells in constitutive Tcrd-/- mice is functionally compensated by other lymphocytes taking over genuine γδ T cell functions. To test this, we generated a knock-in model for diphtheria toxin-mediated conditional γδ T cell depletion. In contrast to IFN-γ-producing γδ T cells, IL-17-producing γδ T cells (Tγδ17 cells) recovered inefficiently after depletion, and their niches were filled by expanding Th17 cells and ILC3s. Complementary genetic fate mapping further demonstrated that Tγδ17 cells are long-lived and persisting lymphocytes. Investigating the function of γδ T cells, conditional depletion but not constitutive deficiency protected from imiquimod-induced psoriasis. Together, we clarify that fetal thymus-derived Tγδ17 cells are nonredundant local effector cells in IL-17-driven skin pathology.