Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells

Nat Immunol. 2009 Aug;10(8):857-63. doi: 10.1038/ni.1767. Epub 2009 Jul 5.

Abstract

Interleukin 22 (IL-22) is a cytokine produced by the T(H)-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4(+) T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-gamma (IFN-gamma). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the T(H)-17 and T helper type 1 (T(H)1) transcription factors RORgammat and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor-dependent way. Our findings delineate a previously unknown subset of human CD4(+) effector T cells dedicated to skin pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • Humans
  • Immunologic Memory
  • In Vitro Techniques
  • Interleukin-17 / biosynthesis*
  • Interleukin-22
  • Interleukins / biosynthesis*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, CCR10 / metabolism
  • Receptors, CCR4 / metabolism
  • Receptors, CCR6 / metabolism
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • Skin / immunology*
  • T-Box Domain Proteins / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*

Substances

  • CCR10 protein, human
  • CCR4 protein, human
  • CCR6 protein, human
  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, CCR10
  • Receptors, CCR4
  • Receptors, CCR6
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • T-Box Domain Proteins
  • T-box transcription factor TBX21