Induced IL-17-producing invariant NKT cells require activation in presence of TGF-β and IL-1β

J Immunol. 2013 Jan 15;190(2):805-11. doi: 10.4049/jimmunol.1201010.

Abstract

IL-17 production by innate-like lymphocytes, including γδ and invariant NKT (iNKT) cells, have been ascribed to specific lineages that are endowed with this functional specialization during thymic differentiation. IL-17-producing iNKT cells have been described as a CD4(-)NK1.1(-) lineage in mice and CD161(+) in humans. We found that, in mice, noncommitted iNKT cells can be induced to produce IL-17 when activated in presence of TGF-β and IL-1β. This peripheral induction of IL-17 expression could be observed in any subset irrespectively of CD4 and NK1.1 expression, the process leading to loss of NK1.1 expression and partial CD4 downmodulation. Furthermore, induced IL-17-producing iNKT cells were sufficient to drive neutrophilic airways inflammation upon intratracheal adoptive cell transfer into congenic mice. Taken together, our data show that similarly to regulatory T cells, which have a natural and peripherally induced subset, IL-17 production by iNKT cells can also be imprinted in natural iNKT17 cells or peripherally induced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-17 / biosynthesis*
  • Interleukin-1beta / pharmacology*
  • Interleukin-6 / pharmacology
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology*
  • Mice
  • Natural Killer T-Cells / drug effects*
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Neuropilin-1 / metabolism
  • Neutrophils / immunology
  • Respiratory System / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-6
  • Transforming Growth Factor beta
  • Neuropilin-1