Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes

Calcium (Ca(2+)) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca(2+) is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca(2+) has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca(2+) can enter the cytoplasm either from intracellular stores or from outside the cells when Ca(2+) permeable ion channels in the plasma membrane open. The Ca(2+) release-activated (CRAC) channel is the most prominent Ca(2+) ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca(2+) sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca(2+) channels in the plasma membrane are the voltage-gated Ca(2+) (Ca(V)) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca(V) gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca(2+) channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V) 2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca(V) genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.