title: Vitamin D receptor activation improves allergen-triggered eczema in mice.
abstract: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has increased in prevalence over the last several decades in industrialized countries. AD is a multifactorial, heterogenous disease with a variety of defects in the immune system, in antimicrobial defense mechanisms and epidermal barrier integrity, which collectively contribute to the risk and severity of AD development. Vitamin D receptor (VDR) signaling has been shown to be important not only in the immune system but also in the skin and in particular keratinocytes to regulate skin homeostasis and epidermal barrier function. However, this work aimed to analyze the role and clinical efficiency of VDR activation by a VDR agonist without calcium-mobilizing activity in a mouse model of allergen-triggered eczema. We show that the systemic administration of the low-calcemic VDR agonist significantly improved the allergen-triggered eczema. Thereby, forkhead box P3 (Foxp3)-expressing regulatory T cells, revealed to have a role in AD, were selectively increased in the skin of VDR agonist-treated mice. Moreover, our results demonstrate a marked induction of skin barrier gene and antimicrobial peptide gene expression in skin lesions of VDR agonist-treated mice. Thus, our study provides evidence that systemic VDR agonist treatment may improve allergen-triggered eczema in vivo.
authors.affiliation: Allergie-Centrum-Charité, CCM, Klinik für Dermatologie und Allergologie, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Hartmann
authors.forename: René
authors.initials: R
authors.lastname: Riedel
authors.forename: Katharina
authors.initials: K
authors.lastname: Jörss
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Andreas
authors.initials: A
authors.lastname: Steinmeyer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zügel
authors.forename: Magda
authors.initials: M
authors.lastname: Babina
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000209:etiology; D004485:Eczema / Q000188:drug therapy*; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008807:Mice, Inbred BALB C; D018167:Receptors, Calcitriol / Q000819:agonists / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000485:Allergens; D023181:Antimicrobial Cationic Peptides; D018167:Receptors, Calcitriol