Effects of 1,25-Dihydroxyvitamin D₃ on in vitro Lymphocyte Reactions: Arguments for a Role at the Maternofetal Interface

Abstract

Calcitriol or 1,25-dihydroxyvitamin D₃ is synthesized by successive hydroxylations of vitamin D in the liver and kidney and during pregnancy in the placenta and the decidua. The aim of the present study was to clarify the immunoregulatory role of calcitriol, if any, during pregnancy. Calcitriol concentrations of 10^–10 to 10^–8M was shown to reduce the proliferation of allogeneically stimulated lymphocytes and cytotoxic cell generation in a dose-dependent manner. However, calcitriol did not inhibit IL-2-dependent proliferation of CTLL-2 cell line. Calcitriol reduced non-MHC restricted cytotoxicity. Calcitrioltherefore, might be involved in the successful engraftment and growth of the fetoplacental unit possibly synergized with other products of placental or decidual origin.

Vitamin D and Multiple Sclerosis

“…The induction of the 1a-hydroxylase in decidual macrophages [180], together with the epigenetic decoupling of vitamin D feedback catabolism [265], maximizes the bioavailability of 1,25(OH) 2 D 3 at the border between mother and fetus. The 1,25(OH) 2 D 3 (and estrogen) may modulate the activity of T lymphocytes specific for paternal antigens to maintain the immune tolerance needed for successful gestation [180,266]. The dramatic increase in circulating 1,25(OH) 2 D 3 (and estrogen) during pregnancy may also modulate the activity of T lymphocytes specific for neural antigens, thereby restoring immune self tolerance and reducing MS attacks during pregnancy [163].…”

Extrarenal 1α-Hydroxylase

“…Instead, the presence of VDR in the placenta suggests that vitamin D functions in an intracrine fashion at the fetalematernal interface [121]. One possible explanation is that 1,25(OH) 2 D acts as a regulator of placental calcium transport [121], but an immunomodulatory role has also been proposed [122]. The latter stems, in part, from studies highlighting immune activity within the heterogeneous cells that make up the placenta.…”

Vitamin D and Human Pregnancy

“…In a similar fashion, CYP27B1 expression has been reported in the gastrointestinal (GI) tract 25 , and this may play a role in mediating immune responses and protection against inflammation within the GI tract 140,141 . With these observations in mind, several previous reviews have postulated that CYP27B1 may fulfill a similar barrier function during pregnancy 29,110,142 . The remainder of this section will review the evidence to support this proposal.…”

“…Instead, the presence of VDR in the placenta has highlighted potential autocrine or paracrine functions for vitamin D at the fetal-maternal interface 109 . One possible explanation is that 1,25(OH) 2 D acts as a locally synthesized regulator of placental calcium transport 109 , but an immunmodulatory function has also been proposed 110 114,115 immunity, and thus it is possible that vitamin D will exert effects on a variety of responses during pregnancy, including implantation, as well as responses to infection and inflammation. Indeed, expression of VDR and CYP27B1 has been reported in many tissues that can be broadly termed 'barrier sites' 116,117 , indicating that localized responses to vitamin D may be a key feature of these tissues.…”