Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients
T helper 17 (Th17) cells and regulatory T (Treg) cells are two distinct subsets of CD4(+) T cells which have opposite effects on inflammation, autoimmunity and immunological rejection of foreign tissue. Treg cells have been shown to be important in maintaining materno-fetal tolerance, but the role of Th17 cells in human pregnancy and pathological pregnancy, especially in relation to unexplained recurrent spontaneous abortion (RSA), has not been investigated. In this study, we showed that the proportion of Th17 cells in the peripheral blood and decidua was significantly higher in unexplained RSA patients compared to normal, early pregnant women. Meanwhile, there was an inverse relationship between Th17 cells and Treg cells in the peripheral blood lymphocytes (PBL) and decidua in unexplained RSA. The expression of Th17 related factors, IL-17, IL-23 and retinoid orphan nuclear receptor (RORC), in PBL and decidua in unexplained RSA patients was significantly higher than normal, early pregnant women. This study is the first to define the occurrence of Th17 cells in unexplained RSA patients and in normal, early pregnant women. We suggest that these highly pro-inflammatory cells contribute to unexplained RSA, and the balance between Th17 cells and Treg cells may be critical to pregnancy outcomes.
Available from: Tom Kieffer
- "Other evidence implying Treg cells in the pathophysiology of recurrent miscarriage are altered Treg/ Th17 balances found in recurrent miscarriage. Higher levels of Th17 cells and Th17 associated cytokines have been found in decidual tissue and peripheral blood of women with recurrent miscarriage  , indicating an imbalance between Treg and Th17 cells in these women . Most likely the regulation of this balance is dysfunctional, as it has been shown that peripheral blood mononuclear cells from women with recurrent miscarriage show greater proliferation of Th17 and fewer Treg cells once cultured in the presence of sperm antigens from their male partner . "
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ABSTRACT: Recurrent miscarriage is a reproductive disorder affecting many couples. Although several factors are associated with recurrent miscarriage, in more than 50% of the cases the cause is unknown. Maladaptation of the maternal immune system is associated with recurrent miscarriage and could explain part of its pathophysiology. Modulating the maternal immune system toward pregnancy tolerance could benefit pregnancy outcome. Although there is a clear scientific rationale that modulating the maternal immune system could benefit recurrent miscarriage, only a few studies suggest possible beneficial effects of immune modulators as a therapy for recurrent miscarriage. Therapies skewing the maternal immune response to a tolerating regulatory T cell rich environment seem especially promising; however, more research is needed to find effective and safe maternal immune modulators for reproductive pathologies as recurrent miscarriage. Moreover, the possible side effects on maternal, fetal, and neonatal immune function are essentially unknown, and its elucidation is crucial before any possible therapeutic strategies could be clinically implemented.
European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2014; 181. DOI:10.1016/j.ejogrb.2014.07.038 · 1.70 Impact Factor
Available from: Vincent Geenen
- "The proportion of Th17 cells has been shown to be higher in blood and decidua of patients with unexplained recurrent spontaneous abortion (51, 52). Th17 factors like RORc and IL-17 are also higher in deciduas of those women. "
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ABSTRACT: Acceptance of the fetal semi-allograft by the mother's immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has been expanded to include CD4+ regulatory T (Treg) and T helper 17 (Th17) cells. Pregnancy hormones exert very significant modulatory properties on the maternal immune system. In this review, we describe mechanisms by which the endocrine milieu modulates CD4 T cell polarization during pregnancy. We first focused on Treg and Th17 cells and on their importance for pregnancy. Secondly, we review the effects of pregnancy hormones [progesterone (P4) and estradiol (E2)] on immune cells previously described, with a particular attention to human chorionic gonadotropin (hCG). The importance of Treg cells for pregnancy is evidenced. They are recruited before implantation and are essential for pregnancy maintenance. Decreased number or less efficient Treg cells are implicated in fertility disorders. As for Th17 cells, the few available studies suggest that they have a negative impact on fertility. Th17 frequency is increased in infertile patients. With the combination of its pro-effects on Th2 and Treg cells and anti-effects on Th1 and Th17 cells, P4 contributes to establishment of a favorable environment for pregnancy. E2 effects are more dependent on the context but it seems that E2 promotes Treg and Th2 cells while it inhibits Th1 cells. hCG positively influences activities of Treg and uterine natural killer cells. This embryo signal is an essential actor for the success of pregnancy, both as the endocrine factor regulating P4 secretion by the ovarian corpus luteum, but also as a paracrine agent during implantation as well as an angiogenic and immunologic mediator during the course of gestation. Luteinizing hormone (LH) immune properties begin to be studied but its positive impact on Treg cells suggests that LH could be a considerable immunomodulator in the mouse.
Frontiers in Endocrinology 07/2014; 5:106. DOI:10.3389/fendo.2014.00106
Available from: Alfredo Perales
- "Th17 cells secrete IL-17 and express CC chemokine receptor type 6 (CCR6) . Whereas the prevalence of Tregs lowered, that of Th17 cells increased in both the peripheral blood and decidua of patients with unexplained recurrent miscarriage as compared to healthy early pregnant women . Interestingly, the IL-17 expression can be inhibited by Treg. "
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ABSTRACT: Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous or in vitro fertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies and in vitro fertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.
Research Journal of Immunology 06/2014; 2014:210241. DOI:10.1155/2014/210241
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