title: Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies.
abstract: Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD. Upon activation of the ORAI1 calcium channel, atopic epidermis releases large amounts of thymic stromal lymphopoietin (TSLP), which initiates the Th2 and Th22 immune response. Th2-derived interleukin-31 and TSLP induce an itch sensation. Taken together, TSLP/Th2/Th22 pathway is a promising target for developing new therapeutics for AD. Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD.
authors.affiliation: Department of Dermatology, Kyushu University, Fukuoka, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan; Division of Skin Surface Sensing, Department of Dermatology, Kyushu University, Fukuoka, Japan. Electronic address: furue@dermatol.med.kyushu-u.ac.jp.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.affiliation: Department of Dermatology, Kyushu University, Fukuoka, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Dermatology, Kyushu University, Fukuoka, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Tsuji
authors.affiliation: Department of Dermatology, Kyushu University, Fukuoka, Japan.
authors.forename: Dugarmaa
authors.initials: D
authors.lastname: Ulzii
authors.affiliation: Department of Dermatology, Kyushu University, Fukuoka, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kido-Nakahara
authors.affiliation: Department of Dermatology, Kyushu University, Fukuoka, Japan; Division of Skin Surface Sensing, Department of Dermatology, Kyushu University, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakahara
authors.affiliation: Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015551:Autoimmunity; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D000091344:Filaggrin Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D015395:Histocompatibility Antigens Class I; D018836:Inflammation Mediators; C089395:T22 antigen; D007073:Immunoglobulin E
keywords: Atopic dermatitis; Filaggrin; IgE autoreactivity; Th2; Th22