Research Article Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation Shelley Gorman, Sian Geldenhuys, Melinda Judge, Clare E. Weeden, Jason Waithman, and Prue H. Hart Telethon Kids Institute, University of Western Australia, Perth, WA, Australia Correspondence should be addressed to Shelley Gorman; shelley.gorman@telethonkids.org.au Received 12 June 2016; Revised 4 August 2016; Accepted 17 August 2016 Academic Editor: Manoj K. Mishra Copyright © 2016 Shelley Gorman et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Skin infammatory responses in individuals with allergic dermatitis may be suppressed by dietary vitamin D through induction and upregulation of the suppressive activity of regulatory T (T Reg ) cells. Vitamin D may also promote T Reg cell tropism to dermal sites. In the current study, we examined the capacity of dietary vitamin D 3 to modulate skin infammation and the numbers and activity of T Reg cells in skin and other sites including lungs, spleen, and blood. In female BALB/c mice, dietary vitamin D 3 suppressed the efector phase of a biphasic ear swelling response induced by dinitrofuorobenzene in comparison vitamin D 3 -defcient female BALB/c mice. Vitamin D 3 increased the percentage of T Reg (CD3+CD4+CD25+Foxp3+) cells in the skin-draining lymph nodes (SDLN). Te suppressive activity of T Reg cells in the SDLN, mesenteric lymph nodes, spleen, and blood was upregulated by vitamin D 3 . However, there was no diference in the expression of the naturally occurring T Reg cell marker, neuropilin, nor the expression of CCR4 or CCR10 (skin-tropic chemokine receptors) on T Reg cells in skin, SDLN, lungs, and airway-draining lymph nodes. Tese data suggest that dietary vitamin D 3 increased the percentages and suppressive activity of T Reg cells in the SDLN, which are poised to suppress dermal infammation. 1. Introduction Vitamin D plays an intrinsic role in shaping innate and adaptive immune responses [1, 2]. Vitamin D is produced following skin exposure to ultraviolet B photons of sunlight, resulting in the conversion of the precursor 7-dehydro- cholesterol into vitamin D 3 , which can also be acquired through dietary supplementation. Te vitamin D-binding protein (VDBP) transports much of this vitamin D 3 into the liver, where a hydroxylation reaction converts vitamin D 3 into 25-hydroxyvitamin D 3 (25(OH)D 3 ). Tis form of vitamin D 3 is found at nanomolar levels in blood, and because of its relative stability and longer half-life, it is used as a measure of vitamin D sufciency, with 50 nM currently considered the tipping point for insufciency by the National Institute of Health [3] (although this remains controversial [4]). In renal proximal tubule epithelial cells, and other cells including disease-activated macrophages (reviewed in [5]), 25(OH)D 3 is converted into the most active vitamin D metabolite, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). It is this form of vitamin D 3 which has the most potent efects on regulating immune responses, with circulating levels in the picomolar range [1, 6]. Central to the ability of 1,25(OH) 2 D 3 to modulate immune responses are changes to regulatory T cells (T Reg cells) and dendritic cells (DCs) [7]. Topical (skin) application of 1,25(OH) 2 D 3 enhanced the suppressive capacity [8, 9] and proliferative activity [10] of CD4+CD25+Foxp3+ T Reg cells. Stimulation of DCs with bacterial products like lipopolysac- charide or cytokines like transforming growth factor-ß may result in the synthesis of 1,25(OH) 2 D 3 from circulating 25(OH)D 3 , promoting T Reg cell activity (reviewed in [1, 2]). Te VDBP may also play an important role in this process, whereby high afnity VDBP can prevent conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 by DCs and thus their ability to modulate T Reg cell activity [11]. With the right costimulators, Hindawi Publishing Corporation Journal of Immunology Research Volume 2016, Article ID 1426503, 13 pages http://dx.doi.org/10.1155/2016/1426503