Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis

M Li, P Hener, Z Zhang, S Kato… - Proceedings of the …, 2006 - National Acad Sciences
M Li, P Hener, Z Zhang, S Kato, D Metzger, P Chambon
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
We have demonstrated that cytokine thymic stromal lymphopoietin (TSLP), whose
expression is rapidly induced upon keratinocyte-selective ablation of retinoid X receptors
(RXRs)-α and-β in the mouse (RXRαβep−/− mice), plays a key role in initiating a skin and
systemic atopic dermatitis-like phenotype. We show here that topical application of the
physiologically active ligand [1α, 25-(OH) 2D3; calcitriol] of the vitamin D receptor, or of its
low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal …
We have demonstrated that cytokine thymic stromal lymphopoietin (TSLP), whose expression is rapidly induced upon keratinocyte-selective ablation of retinoid X receptors (RXRs) -α and -β in the mouse (RXRαβep−/− mice), plays a key role in initiating a skin and systemic atopic dermatitis-like phenotype. We show here that topical application of the physiologically active ligand [1α,25-(OH)2D3; calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome mimicking that seen in RXRαβep−/− mutants and transgenic mice overexpressing TSLP in keratinocytes. Furthermore, topical application of retinoic acid receptor RARγ-selective agonist BMS961 also induces TSLP expression either on its own or synergistically with 1α,25-(OH)2D3. Our data demonstrate that RXR/vitamin D receptor and RXR/retinoic acid receptor-γ heterodimers and their ligands cell-autonomously control the expression of TSLP in epidermal keratinocytes of the mouse. We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases.
National Acad Sciences