The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells

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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.

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Florian Mair

Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Competing interests
The authors declare that no competing interests exist.
Stefanie Joller

Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Competing interests
The authors declare that no competing interests exist.
Romy Hoeppli

Department of Surgery / Child and Family Research Institute, University of British Columbia, Vancouver, Canada

Competing interests
The authors declare that no competing interests exist.
Lucas Onder

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland

Competing interests
The authors declare that no competing interests exist.
Matthias Hahn

Institute for Molecular Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany

Competing interests
The authors declare that no competing interests exist.
Burkhard Ludewig

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland

Competing interests
The authors declare that no competing interests exist.
Ari Waisman

Institute for Molecular Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany

Competing interests
The authors declare that no competing interests exist.
Burkhard Becher

Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

For correspondence
becher@immunology.uzh.ch

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were approved by local authorities (Swiss cantonal veterinary office Zurich, KVET license numbers 86/2012, 70/2015, 100/2015 and 68/2013) and performed in strict accordance with the corresponding license.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.