Abstract
Signaling pathways of the vitamin D receptor (VDR) and the triggering receptor expressed on myeloid cells (TREM) have been independently implicated in the biology of numerous of cutaneous pathologies. There is substantial evidence for possible crosstalk between these pathways, though the relationship between VDR and TREMs remains unclear. In this study, we characterize the effects of vitamin D-deficiency and sufficiency on the cutaneous expression of TREM-1, TREM-2, VDR, HMGB1, and RAGE. Cutaneous tissue isolated from Yucatan microswine were immunohistochemically evaluated for epidermal expression of TREM-1, TREM-2, VDR, HMGB1, and RAGE. The swine were fed a vitamin D-deficient or vitamin D-sufficient diet to examine the role of vitamin D state on levels of these markers. In vitamin D-sufficient animals, keratinocytes exhibited elevated levels of TREM-1, TREM-2. Additionally, TREM-1 expression predominated in basal cells, whereas TREM-2 levels were higher in keratinocytes, regardless of vitamin D state. Levels of HMGB1 and RAGE did not differ by vitamin D state. VDR expression was consistently higher in the cytoplasm and nuclei of basal cells, when compared to keratinocytes. Our findings suggest a role of vitamin D in signaling of TREM pathways. Additionally, the TREM ratio may play a role in keratinocyte differentiation and should be explored further. Possible signaling crosstalk between these pathways has a potential role in progression of cutaneous malignancies and other inflammatory pathologies.