Article abstract
Nature Immunology 8, 950 - 957 (2007)
Published online: 5 August 2007 | doi:10.1038/ni1497
Development, cytokine profile and function of human interleukin 17–producing helper T cells
Nicholas J Wilson1, Katia Boniface1, Jason R Chan1,4, Brent S McKenzie1, Wendy M Blumenschein2, Jeanine D Mattson2, Beth Basham2, Kathleen Smith2, Taiying Chen2, Franck Morel3, Jean-Claude Lecron3, Robert A Kastelein1, Daniel J Cua1, Terrill K McClanahan2, Edward P Bowman1 & Rene de Waal Malefyt1
Abstract
TH-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the TH-17 lineage is dependent on transforming growth factor-
and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1 induced the development of human TH-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-
, the chemokine CCL20 and transcription factor RORt. In situ, TH-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 TH-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse TH-17 cells require distinct factors during differentiation and that human TH-17 cells may regulate innate immunity in epithelial cells.
- Department of Discovery Research, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, California 94304-1104, USA.
- Department of Experimental Pathology and Pharmacology, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, California 94304-1104, USA.
- Laboratoire Cytokines et Inflammation EA 3806, Universite de Poitiers, Centre Hospitalier Universitaire de Poitiers, Pole Biologie Sante, Pineau, 86022 Poitiers, France.
- Present address: Entelos, Foster City, California 94404, USA.
Correspondence to: Rene de Waal Malefyt1 e-mail: rene.de.waal.malefyt@spcorp.com
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