Proinflammatory environment dictates the IL-17-producing capacity of human invariant NKT cells

J Immunol. 2011 May 15;186(10):5758-65. doi: 10.4049/jimmunol.1003043. Epub 2011 Apr 8.

Abstract

CD1d-reactive invariant NKT (iNKT) cells have been implicated in a number of experimental models of human pathologies. Given the scope of their immunoregulatory activities mediated through distinct cytokine patterns, it has been proposed that this functional diversity originates from distinct iNKT subpopulations. In this study, we report that human CD161(+) iNKT cells are intrinsically endowed with the capacity to generate IL-17, but require TGF-β, IL-1β, and IL-23 to carry out this potential. IL-17-producing iNKT cells are already present in cord blood but, in contrast to peripheral blood iNKT cells, they cannot generate IFN-γ. These IL-17 producers respond to aryl hydrocarbon receptor stimulation and express IL-23 receptor and retinoic acid-related orphan receptor C, similar to conventional T helper 17 cells, from which they differ by their restricted ability to coproduce IL-22. In conclusion, IL-17 production by human iNKT cells depends on two critical parameters, namely an intrinsic program and a proinflammatory environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Inflammation / immunology*
  • Interferon-gamma
  • Interleukin-17 / biosynthesis*
  • Interleukin-1beta / biosynthesis
  • Interleukin-22
  • Interleukin-23 / biosynthesis
  • Interleukins / biosynthesis
  • NK Cell Lectin-Like Receptor Subfamily B / immunology
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon / metabolism
  • Receptors, Interleukin / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • Transforming Growth Factor beta / biosynthesis

Substances

  • IL23R protein, human
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Interleukins
  • NK Cell Lectin-Like Receptor Subfamily B
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Aryl Hydrocarbon
  • Receptors, Interleukin
  • Transforming Growth Factor beta
  • Interferon-gamma