Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues

Nat Immunol. 2013 Mar;14(3):221-9. doi: 10.1038/ni.2534. Epub 2013 Jan 20.

Abstract

Innate lymphoid cells (ILCs) are effectors of innate immunity and regulators of tissue modeling. Recently identified ILC populations have a cytokine expression pattern that resembles that of the helper T cell subsets T(H)2, T(H)17 and T(H)22. Here we describe a distinct ILC subset similar to T(H)1 cells, which we call 'ILC1'. ILC1 cells expressed the transcription factor T-bet and responded to interleukin 12 (IL-12) by producing interferon-γ (IFN-γ). ILC1 cells were distinct from natural killer (NK) cells as they lacked perforin, granzyme B and the NK cell markers CD56, CD16 and CD94, and could develop from RORγt(+) ILC3 under the influence of IL-12. The frequency of the ILC1 subset was much higher in inflamed intestine of people with Crohn's disease, which indicated a role for these IFN-γ-producing ILC1 cells in the pathogenesis of gut mucosal inflammation.

MeSH terms

  • Animals
  • CD56 Antigen / analysis
  • Cell Differentiation
  • Cells, Cultured
  • Colitis / immunology
  • Crohn Disease / immunology*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Granzymes / analysis
  • Humans
  • Inflammation
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestines / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily D / analysis
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Perforin / analysis
  • Receptors, IgG / analysis
  • T-Box Domain Proteins / biosynthesis*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism

Substances

  • CD56 Antigen
  • Cytokines
  • NK Cell Lectin-Like Receptor Subfamily D
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, IgG
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Perforin
  • Interleukin-12
  • Interferon-gamma
  • Granzymes