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

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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.

In: J EXP MED, Vol. 215, No. 12, 03.12.2018, p. 3006-3018.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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 2018, 'Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells', J EXP MED, vol. 215, no. 12, pp. 3006-3018. https://doi.org/10.1084/jem.20181439

APA

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. (2018). Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells. J EXP MED, 215(12), 3006-3018. https://doi.org/10.1084/jem.20181439

Vancouver

Sandrock I, Reinhardt A, Ravens S, Binz C, Wilharm A, Martins J et al. Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells. J EXP MED. 2018 Dec 3;215(12):3006-3018. https://doi.org/10.1084/jem.20181439

Bibtex

@article{f1779df9c5fa4cc4a5ad29230e2f6664,
title = "Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells",
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.",
keywords = "Animals, Interferon-gamma/genetics, Mice, Mice, Knockout, Models, Genetic, Models, Immunological, Receptors, Antigen, T-Cell, gamma-delta/genetics, Skin/immunology, Th17 Cells/immunology",
author = "Inga Sandrock and Annika Reinhardt and Sarina Ravens and Christoph Binz and Anneke Wilharm and Joana Martins and Linda Oberd{\"o}rfer and Likai Tan and Stefan Lienenklaus and Baojun Zhang and Ronald Naumann and Yuan Zhuang and Andreas Krueger and Reinhold F{\"o}rster and Immo Prinz",
note = "{\textcopyright} 2018 Sandrock et al.",
year = "2018",
month = dec,
day = "3",
doi = "10.1084/jem.20181439",
language = "English",
volume = "215",
pages = "3006--3018",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells

AU - Sandrock, Inga

AU - Reinhardt, Annika

AU - Ravens, Sarina

AU - Binz, Christoph

AU - Wilharm, Anneke

AU - Martins, Joana

AU - Oberdörfer, Linda

AU - Tan, Likai

AU - Lienenklaus, Stefan

AU - Zhang, Baojun

AU - Naumann, Ronald

AU - Zhuang, Yuan

AU - Krueger, Andreas

AU - Förster, Reinhold

AU - Prinz, Immo

N1 - © 2018 Sandrock et al.

PY - 2018/12/3

Y1 - 2018/12/3

N2 - 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.

AB - 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.

KW - Animals

KW - Interferon-gamma/genetics

KW - Mice

KW - Mice, Knockout

KW - Models, Genetic

KW - Models, Immunological

KW - Receptors, Antigen, T-Cell, gamma-delta/genetics

KW - Skin/immunology

KW - Th17 Cells/immunology

U2 - 10.1084/jem.20181439

DO - 10.1084/jem.20181439

M3 - SCORING: Journal article

C2 - 30455268

VL - 215

SP - 3006

EP - 3018

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 12

ER -