Development, cytokine profile and function of human interleukin 17-producing helper T cells.
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.
Wilson
Nicholas J
NJ
Department of Discovery Research, Schering-Plough Biopharma (formerly DNAX Research), Palo Alto, California 94304-1104, USA.
Boniface
Katia
K
Chan
Jason R
JR
McKenzie
Brent S
BS
Blumenschein
Wendy M
WM
Mattson
Jeanine D
JD
Basham
Beth
B
Smith
Kathleen
K
Chen
Taiying
T
Morel
Franck
F
Lecron
Jean-Claude
JC
Kastelein
Robert A
RA
Cua
Daniel J
DJ
McClanahan
Terrill K
TK
Bowman
Edward P
EP
de Waal Malefyt
Rene
R
D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23