RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells

Nat Immunol. 2009 Jan;10(1):83-91. doi: 10.1038/ni.1684. Epub 2008 Nov 23.

Abstract

The mucosal immune system of the intestine is separated from a vast array of microbes by a single layer of epithelial cells. Cues from the commensal microflora are needed to maintain epithelial homeostasis, but the molecular and cellular identities of these cues are unclear. Here we provide evidence that signals from the commensal microflora contribute to the differentiation of a lymphocyte population coexpressing stimulatory natural killer cell receptors and the transcription factor RORgammat that produced interleukin 22 (IL-22). The emergence of these IL-22-producing RORgammathiNKp46+NK1.1(int) cells depended on RORgammat expression, which indicated that these cells may have been derived from lymphoid tissue-inducer cells. IL-22 released by these cells promoted the production of antimicrobial molecules important in the maintenance of mucosal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / immunology
  • Bacteria / immunology
  • Cell Differentiation
  • Homeostasis / immunology
  • Interleukins / biosynthesis
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Mice
  • Mice, Knockout
  • Natural Cytotoxicity Triggering Receptor 1 / immunology
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Peyer's Patches / immunology
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / physiology*
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / physiology*
  • Transcription Factors / physiology*

Substances

  • Antigens, Ly
  • Interleukins
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Transcription Factors
  • interleukin-22