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

Affiliation

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.

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