title: Development of a novel Ag-specific immunotherapy using CpG oligodeoxynucleotides in a new, unique mouse cutaneous eosinophilic inflammation model.
abstract: The number of patients with severe atopic dermatitis (AD) has been on the rise recently. We are therefore urgently in need of a treatment that can suppress Th2 cell-mediated responses in an Ag-specific fashion. Oligodeoxynucleotides (ODN)containing CpG motifs (CpG ODN) have been highlighted as immunomodulators that reduce Th2-mediated responses. To determine the effect of CpG ODN on Th2-mediated skin inflammation, we first developed a reproducible murine model of protein Ag-induced eosinophilic inflammation that is accompanied by epidermal acanthosis and increased serum IgE levels as seen in AD. In this model we found that treatment with CpG ODN during epicutaneous sensitization in previously i.p.-primed mice prevented the development of Th2-mediated responses. Furthermore, to evaluate the therapeutic effect of CpG ODN on established eosinophilic inflammation, mice were treated with a course of the immunotherapy at a skin site remote from the area of Ag application prior to the second 1-wk epicutaneous exposure to Ag. Therapeutic treatment with CpG ODN plus Ag, but not that with CpG ODN alone, could reverse the established eosinophilic inflammation. The presented results provide strong evidence for the feasibility of a novel Ag-specific immunomodulator to treat cutaneous eosinophilic inflammation such as that characteristically found in patients with severe AD.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tanawatt
authors.initials: T
authors.lastname: Kootiratrakarn
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.forename: Kunio
authors.initials: K
authors.lastname: Sano
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Okuyama
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.forename: Hachiro
authors.initials: H
authors.lastname: Tagami
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terui
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007136:Immunoglobulins / Q000097:blood; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000627:therapeutic use*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007136:Immunoglobulins; D018836:Inflammation Mediators; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D010047:Ovalbumin