Data Availability StatementAll relevant data are contained inside the paper. band of 33 initial trimester women that are pregnant with repeated miscarriage and in several 20 healthy women that are pregnant in the initial trimester of regular being pregnant. Among mononuclear cells isolated from peripheral blood, the populations of DCs and TREGs were assessed by circulation cytometry. The percentage of myeloid DCs and lymphoid DCs showed no significant difference between study and control group. Necrostatin-1 tyrosianse inhibitor Older maternal age and obesity significantly reduced the Necrostatin-1 tyrosianse inhibitor pool of circulating myeloid and lymphoid DCs (R=-0.39, p=0.02). Necrostatin-1 tyrosianse inhibitor In miscarriages the percentage of circulating TREGs was significantly lower compared to normal pregnancies (p=0.003). Among the analysed factors the percentage of TREGs was the most sensitive and the most specific parameter which correlated with the pregnancy loss. The reduction in the population of circulating TREGs suggests immunoregulatory mechanisms disorder inside a pregnancy complicated by miscarriage. Intro Miscarriage is one of the most common complications of pregnancy. The loss of pregnancy before 22 weeks of its duration affects approximately 15C20% of clinically confirmed pregnancies, but the actual percentage of early pregnancy loss has not been precisely identified [1]. Recurrent miscarriage, defined as the loss of three or more consecutive pregnancies, affects about 1C2% of couples [2]. The causes of recurrent miscarriages include (apart from genetic, anatomical, infectious, hormonal or metabolic factors) disorders of auto- and alloimmune source. However, in about 40C50% of miscarriages no cause can be recognized and such instances are classified as idiopathic [3]. This group may include a variety of disorders of maternal immune response to paternal alloantigens located on the surface of trophoblast and fetal cells. The mechanisms allowing mother to Rabbit Polyclonal to OR10Z1 keep up the alloantigenic pregnancy and fetus to develop properly are still the subject of many studies. For many years pregnancy was regarded as a state of immune suppression. According to modern knowledge, the maintenance of pregnancy is possible due to immunological tolerance [4C5]. CD4+ T cells exhibiting a constant manifestation of interleukin-2 Necrostatin-1 tyrosianse inhibitor (CD25) chain receptor are responsible for maintaining peripheral immunological self-tolerance and are called regulatory T cells (TREGs) [6]. It is a heterogenous group of cells, the best known of which are lymphocytes T CD4+CD25+ expressing the transcription factor Foxp3. Such cells are characterized by high expression of CD25. Forkhead box P3 (FoxP3) expression in TREG cells is believed to be a critical factor in the maintenance of TREG cells suppressive function [7]. These lymphocytes differentiate in the thymus into so-called natural TREGs. However, under the influence of cytokines or after contact with an antigen the regulatory T cells may also be formed peripherally [8,9]. Multiple mechanisms of action of TREGs have been proposed, including cell contact dependent and cytokine dependent mechanisms. Dendritic cells (DC) are the cells responsible for professional antigen presentation to T cells and play a significant role in activation, polarization and regulation of the immune response [10]. Two main subtypes of dendritic cells can be distinguished in human blood: myeloid DCs (mDCs) and lymphoid/ plasmacytoid DCs (pDCs). mDCs are the main subgroup in peripheral blood involved in stimulation of T cells. pDCs are components of the innate immune system, produce large amounts of type I interferon. Upon subsequent activation these cells can promote Th2 type immune response. Circulating dendritic cells do not have all the typical features of their counterparts in tissue and they are less mature. Recruitment, activation and expansion of T cells depend on the maturity of DCs. The differentiation of CD4 + T cells occurring in the presence of immature dendritic cells results in stimulation of the immune response and developing.