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

Author:

Sandrock Inga1,Reinhardt Annika1,Ravens Sarina1,Binz Christoph1,Wilharm Anneke1,Martins Joana1,Oberdörfer Linda1,Tan Likai1,Lienenklaus Stefan12ORCID,Zhang Baojun3,Naumann Ronald4,Zhuang Yuan3,Krueger Andreas1ORCID,Förster Reinhold1,Prinz Immo1ORCID

Affiliation:

1. Institute of Immunology, Hannover Medical School, Hannover, Germany

2. Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany

3. Department of Immunology, Duke University Medical Center, Durham, NC

4. Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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.

Funder

Deutsche Forschungsgemeinschaft

Hannover Biomedical Research School

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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