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RESEARCH PRODUCT
The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells
Florian MairBurkhard LudewigMatthias HahnStefanie JollerRomy E. HoeppliBurkhard BecherLucas OnderAri Waismansubject
MouseT-Lymphocytes10263 Institute of Experimental ImmunologyInterleukin 210302 clinical medicineT-Lymphocyte Subsets2400 General Immunology and MicrobiologyCytotoxic T cellIL-2 receptorBiology (General)0303 health sciencesGeneral NeuroscienceZAP70Interleukin-17QR2800 General NeuroscienceCell DifferentiationReceptors Antigen T-Cell gamma-deltaGeneral MedicineNatural killer T cell3. Good healthCell biologymedicine.anatomical_structureMedicineSignal TransductionResearch ArticleQH301-705.5T cellScienceImmunology610 Medicine & healthProtein Serine-Threonine KinasesBiologyγδ T cellsGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciences1300 General Biochemistry Genetics and Molecular BiologymedicineAnimalsAntigen-presenting cell030304 developmental biologyGeneral Immunology and MicrobiologyNIKT cell developmentT cell cytokine productionthymic stromaMice Inbred C57BLDevelopmental Biology and Stem CellsImmunology570 Life sciences; biology030215 immunologydescription
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. DOI: http://dx.doi.org/10.7554/eLife.10087.001
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-12-05 | eLife |