title: Inducible nitric oxide synthase downmodulates contact hypersensitivity by suppressing dendritic cell migration and survival.
abstract: Nitric oxide (NO) has several important roles in various physiological settings; one of the NO synthases, inducible NO synthase (iNOS), is induced by external stimulation of the skin. A prototypic example of external stimulation is hapten exposure, which induces the T-cell-mediated immune response known as contact hypersensitivity (CHS). We herein report on cutaneous dendritic cell (DC) function in the presence of an iNOS-specific inhibitor during the sensitization phase of CHS. First, we examined epidermal cell (EC) suspensions using flow cytometry with an iNOS antibody and confirmed that iNOS was expressed in the cytoplasm of Langerhans cells (LCs). We then studied the role of iNOS in CHS, and found that responses to DNFB were enhanced by the addition of an iNOS inhibitor during sensitization. Similarly, the iNOS inhibitor augmented FITC-induced migration of cutaneous DCs, including Langerin(+) LCs and Langerin(-) dermal DCs, to draining lymph nodes. Finally, we showed that iNOS inhibitor enhanced LC survival in vitro. We concluded that NO suppresses migration and survival of cutaneous DCs, resulting in a downmodulation of CHS.
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan. k-sugita@med.uoeh-u.ac.jp
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sugita
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yoshiki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ikenouchi-Sugita
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D002633:Chemotaxis; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D003877:Dermatitis, Contact / Q000378:metabolism*; D005260:Female; D007107:Immune System; D015603:Keratinocytes / Q000166:cytology; D007801:Langerhans Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II