Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Sandrock, I; Reinhardt, A; Ravens, S; Binz, C; Wilharm, A; Martins, J; Oberdörfer, L; Tan, L; Lienenklaus, S; Zhang, B; Naumann, R; Zhuang, Y; Krueger, A; Förster, R; Prinz, I
Published Date
- December 3, 2018
Published In
Volume / Issue
- 215 / 12
Start / End Page
- 3006 - 3018
PubMed ID
- 30455268
Pubmed Central ID
- PMC6279411
Electronic International Standard Serial Number (EISSN)
- 1540-9538
Digital Object Identifier (DOI)
- 10.1084/jem.20181439
Language
- eng
Conference Location
- United States