title: Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T cells.
abstract: Increase in the number of patients with atopic dermatitis (AD) has been recently reported. T helper (Th) cells that infiltrate AD skin lesions are Th2-type dominant; reduced exposure to environmental Th1-cytokine-inducing microbes is believed to contribute to the increased number of AD patients. Regulatory type immune responses have been also associated with the occurrence of AD. It has been reported that antigen 85B (Ag85B) purified from mycobacteria is a potent inducer of Th1-type immune response in mice as well as in humans. In this study, we have examined the effect of plasmid DNA encoding Ag85B derived from Mycobacterium kansasii on AD skin lesions induced by oxazolone (OX) application. Th2-cytokine mediated mouse AD model with immediate type response followed by a late phase reaction was developed by repeated applications of low-dose OX to sensitized mice. Mice were immunized with plasmid DNA encoding cDNA of Ag85B before OX sensitization or during repeated elicitation phase. Both therapies were associated with significant suppression of immediate type response, clinical appearance, dermal cell infiltration, reduced IL-4 production, and augmented IFN-gamma mRNA expression compared to placebo-treated mice. Additionally, increased number of Foxp3(+) regulatory T cells were observed in the skin sections in Ag85B treated mice. The results of this study suggest that Ag85B DNA vaccine is a potential therapy for Th2 type dermatitis.
authors.affiliation: Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurokawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mizutani
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000009:adverse effects; D010957:Plasmids / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000473:pathology*; D018418:Th2 Cells / Q000473:pathology*; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019444:Vaccines, DNA; C071448:antigen 85B, Mycobacterium leprae; D010081:Oxazolone; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA