title: Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.
abstract: 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.
authors.affiliation: DNAX, 901 California Avenue, Palo Alto, CA 94304, USA.
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Reche
authors.forename: Holger
authors.initials: H
authors.lastname: Kanzler
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.forename: Gina
authors.initials: G
authors.lastname: Edward
authors.forename: Bernhart
authors.initials: B
authors.lastname: Homey
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
authors.forename: Steve
authors.initials: S
authors.lastname: Ho
authors.forename: Svetlana
authors.initials: S
authors.lastname: Antonenko
authors.forename: Annti
authors.initials: A
authors.lastname: Lauerma
authors.forename: Kathleen
authors.initials: K
authors.lastname: Smith
authors.forename: Daniel
authors.initials: D
authors.lastname: Gorman
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.forename: Jon
authors.initials: J
authors.lastname: Abrams
authors.forename: Satish
authors.initials: S
authors.lastname: Menon
authors.forename: Terri
authors.initials: T
authors.lastname: McClanahan
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal-Malefyt Rd
authors.forename: Fernando
authors.initials: F
authors.lastname: Bazan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kastelein
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: 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
chemical_list: D015415:Biomarkers; D018845:CD11 Antigens; D016207:Cytokines; D015851:Interleukin-7; D012333:RNA, Messenger; D000094632:Thymic Stromal Lymphopoietin