Vitamin D receptor activation improves allergen-triggered eczema in mice

TY - JOUR

T1 - Vitamin D receptor activation improves allergen-triggered eczema in mice

AU - Hartmann, Björn

AU - Riedel, René

AU - Jörss, Katharina

AU - Loddenkemper, Christoph

AU - Steinmeyer, Andreas

AU - Zügel, Ulrich

AU - Babina, Magda

AU - Radbruch, Andreas

AU - Worm, Margitta

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - Allergens/immunology

KW - Animals

KW - Antimicrobial Cationic Peptides/genetics

KW - Dermatitis, Atopic/drug therapy

KW - Eczema/drug therapy

KW - Female

KW - Gene Expression Regulation

KW - Mice

KW - Mice, Inbred BALB C

KW - Receptors, Calcitriol/agonists

KW - T-Lymphocytes/physiology

U2 - 10.1038/jid.2011.296

DO - 10.1038/jid.2011.296

M3 - SCORING: Journal article

C2 - 21938012

VL - 132

SP - 330

EP - 336

JO - J INVEST DERMATOL

JF - J INVEST DERMATOL

SN - 0022-202X

IS - 2

ER -