title: Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines.
abstract: There are immediate, late-phase, and delayed-type reactions to exogenous agents. In IFN-gamma-knockout (IFN-gamma(-/-)) and wild-type B6 mice, we examined the response to picryl chloride (PCl) for assessing delayed-type reactions, and the responses to repeatedly challenged FITC for immediate and late-phase reactions. The delayed-type hypersensitivity was depressed in IFN-gamma(-/-) mice, and the immediate and late-phase reactions were enhanced in IFN-gamma(-/-) mice. As skin-infiltrating lymphocytes were scarce at the PCl-challenged site of IFN-gamma(-/-) mice, we investigated chemokine production by keratinocytes and Langerhans cells (LCs). A real-time PCR analysis demonstrated that Th1 chemokines (CXCL9 and CXCL10) and Th2 chemokines (CCL17 and CCL22) were derived mainly from keratinocytes and LCs, respectively. Challenge with PCl or FITC augmented keratinocyte expression of Th1 chemokines in wild-type but not in IFN-gamma(-/-) mice, and Th2 chemokine production by LCs was induced by repeated FITC in IFN-gamma(-/-) mice. Finally, transfer of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled draining lymph node cells from hapten-sensitized B6 mice or lymph node cells from sensitized green fluorescent protein (GFP) mice to naive IFN-gamma(-/-) mice revealed less infiltration of CFSE(+) or GFP(+) lymphocytes at the challenged site. Our study suggests that one of the crucial actions of IFN-gamma is upregulation of keratinocyte production of Th1 chemokines and downregulation of LC production of Th2 chemokines.
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Yahatanishi, Kitakyushu, Japan. cdm63280@par.odn.ne.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yoshiki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sugita
authors.forename: Noriko
authors.initials: N
authors.lastname: Shiraishi
authors.forename: Ayako
authors.initials: A
authors.lastname: Onoue
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Miwa
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Uki
authors.initials: U
authors.lastname: Yamashita
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018925:Chemokines / Q000235:genetics*; D003877:Dermatitis, Contact / Q000209:etiology*; D005260:Female; D006241:Haptens / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics; D015603:Keratinocytes / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010853:Picryl Chloride / Q000633:toxicity; D054367:Receptors, CXCR3 / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014230:Triazoles / Q000633:toxicity
chemical_list: C521338:4-(1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3,-triazol-4-yl)-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D006241:Haptens; D054367:Receptors, CXCR3; D014230:Triazoles; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010853:Picryl Chloride