RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44

Immunity. 2013 Jun 27;38(6):1223-35. doi: 10.1016/j.immuni.2013.05.013. Epub 2013 Jun 20.

Abstract

RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cellular Microenvironment
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Interleukins / metabolism*
  • Lymphocytes / immunology*
  • Mucous Membrane / immunology
  • Natural Cytotoxicity Triggering Receptor 2 / immunology
  • Natural Cytotoxicity Triggering Receptor 2 / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Receptor Cross-Talk
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Inflammation Mediators
  • Interleukins
  • Natural Cytotoxicity Triggering Receptor 2
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Tumor Necrosis Factor-alpha
  • interleukin-22