title: The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells.
abstract: γδ T cells contribute to first line immune defense, particularly through their ability for rapid production of proinflammatory cytokines. The cytokine profile of γδ T cells is hard-wired already during thymic development. Yet, the molecular pathways underlying this phenomenon are incompletely understood. Here we show that signaling via the NFκB-inducing kinase (NIK) is essential for the formation of a fully functional γδ T cell compartment. In the absence of NIK, development of Vγ5(+) dendritic epidermal T cells (DETCs) was halted in the embryonic thymus, and impaired NIK function caused a selective loss of IL-17 expression by γδ T cells. Using a novel conditional mutant of NIK, we could show in vivo that NIK signaling in thymic epithelial cells is essential for the thymic hardwiring of γδ T cell cytokine production.
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Mair
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Stefanie
authors.identifier: http://orcid.org/0000-0002-6906-4892
authors.initials: S
authors.lastname: Joller
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Romy
authors.initials: R
authors.lastname: Hoeppli
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Onder
authors.affiliation: Institute for Molecular Medicine, University Medical Center, Johannes-Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.affiliation: Institute for Molecular Medicine, University Medical Center, Johannes-Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Burkhard
authors.identifier: http://orcid.org/0000-0002-1541-7867
authors.initials: B
authors.lastname: Becher
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D020381:Interleukin-17 / Q000032:analysis*; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000502:physiology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D020381:Interleukin-17; D017346:Protein Serine-Threonine Kinases; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000097782:NF-kappaB-Inducing Kinase
keywords: Immunology; NIK; T cell development; developmental biology; immunology; mouse; stem cells; thymic stroma; γδ T cells