Development, cytokine profile and function of human interleukin 17-producing helper T cells

Nat Immunol. 2007 Sep;8(9):950-7. doi: 10.1038/ni1497. Epub 2007 Aug 5.

Abstract

T(H)-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the T(H)-17 lineage is dependent on transforming growth factor-beta and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1beta induced the development of human T(H)-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-gamma, the chemokine CCL20 and transcription factor RORgammat. In situ, T(H)-17 cells were identified by expression of the IL-23 receptor and the memory T cell marker CD45RO. Psoriatic skin lesions contained IL-23-producing dendritic cells and were enriched in the cytokines produced by human T(H)-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse T(H)-17 cells require distinct factors during differentiation and that human T(H)-17 cells may regulate innate immunity in epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / biosynthesis
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Cytokines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / biosynthesis*
  • Interleukin-23 / metabolism
  • Polymerase Chain Reaction
  • Psoriasis / immunology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antimicrobial Cationic Peptides
  • Cytokines
  • Interleukin-17
  • Interleukin-23