Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing {gamma}{delta} T cells

T cells are highly conserved in jawed vertebrates, suggesting an essential role in the immune system. However, T cell–deficient Tcrd–/– mice display surprisingly mild phenotypes. We hypothesized that the lack of T cells in constitutive Tcrd–/– mice is functionally compensated by other lymphocytes taking over genuine T cell functions. To test this, we generated a knock-in model for diphtheria toxin–mediated conditional T cell depletion. In contrast to IFN-–producing T cells, IL-17–producing T cells (T17 cells) recovered inefficiently after depletion, and their niches were filled by expanding Th17 cells and ILC3s. Complementary genetic fate mapping further demonstrated that T17 cells are long-lived and persisting lymphocytes. Investigating the function of T cells, conditional depletion but not constitutive deficiency protected from imiquimod-induced psoriasis. Together, we clarify that fetal thymus-derived T17 cells are nonredundant local effector cells in IL-17–driven skin pathology.

Source: The Journal of Experimental Medicine - December 3, 2018 Category: Internal Medicine 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. Tags: Articles Source Type: research