title: The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin.
abstract: Atopic dermatitis is increasing worldwide in correlation with air pollution. Various organic components of pollutants activate the transcription factor AhR (aryl hydrocarbon receptor). Through the use of AhR-CA mice, whose keratinocytes express constitutively active AhR and that develop atopic-dermatitis-like phenotypes, we identified Artn as a keratinocyte-specific AhR target gene whose product (the neurotrophic factor artemin) was responsible for epidermal hyper-innervation that led to hypersensitivity to pruritus. The activation of AhR via air pollutants induced expression of artemin, alloknesis, epidermal hyper-innervation and inflammation. AhR activation and ARTN expression were positively correlated in the epidermis of patients with atopic dermatitis. Thus, AhR in keratinocytes senses environmental stimuli and elicits an atopic-dermatitis pathology. We propose a mechanism of air-pollution-induced atopic dermatitis via activation of AhR.
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Eri H
authors.initials: EH
authors.lastname: Kobayashi
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Okuyama
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.|Tohoku Medical-Megabank Organization, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D000071437:Axon Guidance / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D004817:Epidermis / Q000294:innervation* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D053569:Keratin-15 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011537:Pruritus / Q000276:immunology*; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D051792:Basic Helix-Loop-Helix Proteins; D053569:Keratin-15; D009419:Nerve Tissue Proteins; D036183:Receptor, EphB2; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C490886:ARTN protein, human; C484722:Ahr protein, mouse; C492053:Krt15 protein, mouse; C586311:Ephb2 protein, mouse