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

Published

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

  • 30455268

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20181439

Language

  • eng

Conference Location

  • United States