Journal of Steroid Biochemistry & Molecular Biology 121 (2010) 247–249 Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Immune-modifying properties of topical vitamin D: Focus on dendritic cells and T cells  Shelley Gorman ∗ , Melinda A. Judge, Prue H. Hart Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, Western Australia, Australia article info Article history: Received 15 October 2009 Received in revised form 8 February 2010 Accepted 25 February 2010 Keywords: Vitamin D Skin Skin-draining lymph nodes Dendritic cells T cells abstract Topical creams containing the active form of vitamin D (1,25-dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ) or analogues of this compound are currently used with some success to treat skin conditions including psoriasis and vitiligo. As well as targeting inflammatory processes in the skin, topical application of 1,25(OH) 2 D 3 also affects the function of immune cells in the skin and draining lymph nodes. Topically applied 1,25(OH) 2 D 3 reduces the number of dendritic cells in the skin, resulting in suppressed immu- nity and in particular reduced contact hypersensitivity (CHS) responses. Topical 1,25(OH) 2 D 3 may also promote the migration of dendritic cells from the skin to the draining lymph nodes. Skin application of 1,25(OH) 2 D 3 prevented the inflammatory effects of UVB irradiation on lymph node hypertrophy, when cell numbers were examined 4 days after skin treatment. In contrast, when 1,25(OH) 2 D 3 was applied to UVB irradiated skin, there was no reversal in the suppression of CHS responses caused by UVB irradiation. Instead, 1,25(OH) 2 D 3 had an additive effect with UVB to suppress CHS responses to a greater degree than UVB alone. In these studies, 1,25(OH) 2 D 3 was applied to the treated skin of BALB/c mice immediately fol- lowing UVB irradiation. Finally, topical 1,25(OH) 2 D 3 also enhanced the number and suppressive activity of CD4+CD25+ regulatory T cells in the lymphatic tissue draining skin. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction Vitamin D is an essential hormone synthesised in the skin following the exposure of skin to the UVB wavelengths present in sunlight. The active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D 3 , 1,25(OH) 2 D 3 ), and analogues of this hormone (e.g. calcipotriol, calcipotriene) are successful treatment options for patients with skin diseases such as psoriasis and vitiligo [reviewed by [1]]. Currently, vitamin D is administered topically as a cream directly to diseased skin. The mode by which vita- min D reduces the morbidity of these diseases may occur in part by inhibiting the proliferation and inducing the differenti- ation of keratinocytes in psoriatic lesions [reviewed by [1]]. An alternate pathway whereby topical vitamin D reduces skin inflam- mation is by regulating cells of the immune system, which reside both in the skin, and skin-draining lymph nodes (SDLN). The article reviews the reported effects of topical 1,25(OH) 2 D 3 on  Special issue selected article from the 14th Vitamin D Workshop held at Brugge, Belgium on October 4–8, 2009. ∗ Corresponding author at: Telethon Institute for Child Health Research, Centre for Child Health Research, the University of Western Australia, PO Box 855, West Perth, Western Australia, 6872, Australia. Tel.: +61 8 9489 7884; fax: +61 8 9489 7700. E-mail address: shelleyg@ichr.uwa.edu.au (S. Gorman). immune cells, concentrating on responses by the adaptive arm of the immune response and in particular dendritic cells (DC) and T cells. 2. Topical vitamin D regulates immune cell infiltration into psoriatic lesions Topical calcitriol can modify the accumulation of immune cells within psoriatic plaques. Twice-daily treatment with calcitriol for 4 weeks reduced the proportion of T cells and neutrophils in both the dermis and epidermis of 10 patients with psoriasis [2]. These observations conflict with a report that human T cells treated with 1,25(OH) 2 D 3 (10 nM) in vitro upregulate the chemokine receptor CCR10 and have an enhanced capacity to migrate towards the skin- trophic chemokine CCL27 [3]. 1,25(OH) 2 D 3 (∼40 nM) treatment in vitro also reduced the ability of murine CD4+ T cells to migrate towards stromal cell-derived factor-1 (CXCL12) [4]. 3. Regulation of skin-derived dendritic cells by topical vitamin D Topical 1,25(OH) 2 D 3 regulates skin-derived DC such as Langer- hans cells. Skin DC density and phenotype was assessed in the ear skin of BALB/c mice, which were administered 1,25(OH) 2 D 3 (400 ng/day) once a day for 7 days [5]. The dendritic morphol- 0960-0760/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jsbmb.2010.02.034