Regulatory T-cells and preeclampsia: an overview of literature.

Regulatory T-cells (Tregs) are key players in successful pregnancy and their deficiencies are implicated in pregnancy complications such as preeclampsia (PE), but the results are inconsistent among studies. This study aims to compile an overview of the studies about the associations of Tregs and PE risk and to provide recommendations for future research. A sensitive search of three databases including PubMed, Scopus and Google scholar (from 1995 to January 9, 2015) identified 636 unique titles. An accurate process of study selection, data extraction and method qualification were independently conducted by authors on retrieved papers. Seventeen papers met the inclusion criteria and were included in quality assessment. Regarding the source of Tregs, 14 studies assessed Tregs in peripheral blood, 2 studies in peripheral blood and decidua and one study in peripheral blood and umbilical cord blood. Despite variation in the combinations of markers and other aspects of the studies designs, remarkable constancy in the results of studies that measured Tregs as CD4+FoxP3+ or CD4+CD25+FoxP3+ cells (but not CD4+CD25(high/low)FoxP3+ markers) was found, which in broad terms showed a shift towards fewer Treg cells in PE. This review revealed an association between lower percentage of circulating CD4+FoxP3+ or CD4+CD25+FoxP3+ Tregs and the risk of PE. Given the above issue and regarding the high consistency of studies on reduction of suppressive activity of Tregs in PE, we have proposed a model in which the Tregs deficiency is a reflection of immune endocrine imbalance, which reverses maternal tolerance and results in development of preeclampsia.

FoxP3 gene promoter polymorphism affects susceptibility to preeclampsia.

BACKGROUND: Preeclampsia (PE) is a multifactorial pregnancy disorder and is a major cause of maternal morbidity and mortality. Despite intense study, the pathophysiology of preeclampsia remains enigmatic. Recent studies have reported that regulatory T cells (Tregs) is linked with PE. It is well identified that FoxP3/Scurfin is involved in development and function of Tregs. However, the association between PE and the FoxP3 gene polymorphism has not been sufficiently investigated. In this study, we hypothesized that polymorphisms of the FoxP3 may be related to PE. METHODS: We assessed the relationship between four single-nucleotide polymorphisms (SNPs) in the FoxP3 genes with sequence-specific primers (PCR-SSP) in 81 PE patients and 90 age-matched controls. RESULT: We identified significant difference of rs4824747 GG genotype frequency between the PE and control groups. Women with GG genotypes exhibited higher (OR=6.25, 95% CI=2.63-14.85; P<0.0001) risk of developing PE. None of the other investigated SNPs (rs2232365, rs3761547 and rs3761548) showed significant association with PE. CONCLUSION: We suggest that FoxP3 polymorphisms (rs4824747) could be a potential contributor for the development of PE in Iranian women.

Expression of chemokines and chemokine receptors in brain tumor tissue derived cells.

Chemokine and chemokine receptor expression by tumor cells contributes to tumor growth and angiogenesis and thus these factors may be considered as tumor markers. Here we aimed to characterize cells directly extracted from glioma, meningioma, and secondary brain tumors as well as non-tumoral cells in vitro. Cells were isolated from brain tissues using 0.2% collagenase and characterized by flow cytometry. Expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, MCP-1 and IP-10 was defined using flow cytometry and qRT-PCR methods. Brain tissue isolated cells were observed as spindle-shaped cell populations. No significant differences were observed for expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, and IP-10 transcripts. However, the expression of CXCR4 was approximately 13-fold and 110-fold higher than its counterpart, CXCR7, in meningioma and glioma cells, respectively. CXCR7 was not detectable in secondary tumors but CXCR4 was expressed. In non tumoral cells, CXCR7 had 1.3-fold higher mRNA expression than CXCR4. Flow cytometry analyses of RANTES, MCP- 1, IP-10, CCR5 and CXCR4 expression showed no significant difference between low and high grade gliomas. Differential expression of CXCR4 and CXCR7 in brain tumors derived cells compared to non-tumoral samples may have crucial impacts on therapeutic interventions targeting the SDF-1/CXCR4/CXCR7 axis.