Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.
Whether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (T(H)2)-type allergic inflammation is not known. We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c(+) dendritic cells (DCs) and induced production of the T(H)2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naïve T(H) cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-alpha, while down-regulating IL-10 and interferon-gamma. TSLP was highly expressed by epithelial cells, especially keratinocytes from patients with atopic dermatitis. TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation.
Soumelis
Vassili
V
DNAX, 901 California Avenue, Palo Alto, CA 94304, USA.
Reche
Pedro A
PA
Kanzler
Holger
H
Yuan
Wei
W
Edward
Gina
G
Homey
Bernhart
B
Gilliet
Michel
M
Ho
Steve
S
Antonenko
Svetlana
S
Lauerma
Annti
A
Smith
Kathleen
K
Gorman
Daniel
D
Zurawski
Sandra
S
Abrams
Jon
J
Menon
Satish
S
McClanahan
Terri
T
de Waal-Malefyt Rd
Rene
R
Bazan
Fernando
F
Kastelein
Robert A
RA
Liu
Yong-Jun
YJ
D000328:Adult; D015415:Biomarkers; D018845:CD11 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology* / Q000494:pharmacology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology; D012333:RNA, Messenger; D012867:Skin / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
D015415:Biomarkers; D018845:CD11 Antigens; D016207:Cytokines; D015851:Interleukin-7; D012333:RNA, Messenger; D000094632:Thymic Stromal Lymphopoietin