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.
Nicholas J Wilson  1 ,  Katia Boniface ,  Jason R Chan ,  Brent S McKenzie ,  Wendy M Blumenschein ,  Jeanine D Mattson ,  Beth Basham ,  Kathleen Smith ,  Taiying Chen ,  Franck Morel ,  Jean-Claude Lecron ,  Robert A Kastelein ,  Daniel J Cua ,  Terrill K McClanahan ,  Edward P Bowman ,  Rene de Waal Malefyt
Affiliations
  • 1. Department of Discovery Research, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, California 94304-1104, USA.
PMID: 17676044 DOI: 10.1038/ni1497
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.