title: CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli.
abstract: CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4(+) cells and mast cells infiltrated in Tg mice. Levels of IL-4 mRNA were higher and those of IFN-gamma mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4(+) cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4(+) cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. ytsun-tky@umin.ac.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tsunemi
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Saeki
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagakubo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Shinji
authors.initials: S
authors.lastname: Kagami
authors.forename: Kiyo
authors.initials: K
authors.lastname: Shimazu
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komine
authors.forename: Koji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D003436:Croton Oil / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010080:Oxazoles / Q000494:pharmacology; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C499538:Ccl17 protein, mouse; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D010080:Oxazoles; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D014157:Transcription Factors; C064210:oxazolidine; D015847:Interleukin-4; D003436:Croton Oil; D007371:Interferon-gamma