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

Elife. 2015 Dec 1:4:e10087. doi: 10.7554/eLife.10087.

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.

Keywords: Immunology; NIK; T cell development; developmental biology; immunology; mouse; stem cells; thymic stroma; γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Interleukin-17 / analysis*
  • Mice, Inbred C57BL
  • NF-kappaB-Inducing Kinase
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • Signal Transduction
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / physiology*
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / physiology*

Substances

  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Protein Serine-Threonine Kinases

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.