Endocrine Abstracts

Vitamin D deficiency is prevalent in pregnant women. Active vitamin D (1,25(OH)₂D₃) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) is a potential target for this. CD56⁺ -uterine natural killer (uNK) cells are the most prominent cell type in the decidua during early pregnancy. Given their critical role in foetal implantation and placentation, we hypothesised that uNK cells are a pivotal immunomodulatory target for vitamin D in the placenta. CD56⁺ uNK were isolated from 1st trimester decidua tissue (uNKs)and matched maternal peripheral blood natural killer (pNKs) and stimulated with IL2, IL15, and IL12 in the presence and absence of 1,25(OH)₂D₃ (10 nM). At 24 h, RNA encoding 1-α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), the vitamin D receptor (VDR) and IFN-γ were measured by qPCR and protein expression by flow cytometry. At baseline, both uNK and pNK cells expressed an intracrine vitamin D metabolic system, characterised by CYP27B1, CYP24A1 and VDR. The functionality of this system was demonstrated by both NK cell types as expression of deactivating CYP24A1 (~44- and 85-fold respectively) decreased following 1,25(OH)₂D₃ treatment. In response to cytokines vitamin D activating CYP27B1 and VDR were increased in both NKs, but there was no significant change in CYP24A1. Thus stimulation appears to enhance uNK and pNK responsiveness to intracrine vitamin D. However, in studies of cytokine-induced NK immune function, 1,25(OH)₂D₃ only suppressed inflammatory IFN-γ RNA expression by uNK cells (seven fold) suggesting differential vitamin D sensitivity in uNKs and pNKs. These data show for the first time that uNK cells have a functional vitamin D system, and may be more sensitive to 1,25(OH)₂D₃ than their peripheral blood counterparts.