Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients

Wang, Wen‐Juan; Hao, Cuifang; Yilin,; Yin, Guangwen; Bao, Shihua; Qiu, Lihua; Lin, Qi

doi:10.1016/j.jri.2009.12.003

Cited by 321 publications

(337 citation statements)

References 24 publications

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“…In past research, both IL-23 and IL-17 were reported to be higher in the decidua of patients with RPL compared to normal pregnancy [8,9]. Given these past findings, we expected to see an inverse relationship between IL-22 and IL-17, IL-23.…”

Section: Resultsmentioning

confidence: 84%

“…Once activated, the Th17 cells produce a pro-inflammatory cytokine, IL-17, which acts at the same tissues as IL-22. Previous publications in the reproductive literature have reported higher levels of IL-23 and IL-17 in the decidua of patients with RPL [8,9]. Given these previous findings, we hypothesized that IL-22 and IL-17 are antagonistic in RPL, where IL-22 is tissue protective and IL-17 is destructive.…”

Section: Introductionmentioning

confidence: 68%

“…Although evidence has validated that patients with RPL have abnormal distributions of immune cells in the decidua, it is also likely that the leukocytes present in this patient population exhibit abnormalities in function [6][7][8][9]. This dysfunction may result in abnormal cytokine expression in the decidua of patients with RPL.…”

Section: Introductionmentioning

confidence: 98%

“…More recently, the decidua of patients with RPL have also been evaluated for the presence of T helper (Th) 17 cells. Those patients with RPL have been shown to have higher numbers of Th17 cells in the decidua than a fertile control population [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

Perfetto

Fan

Dahl

et al. 2015

J Assist Reprod Genet

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Purpose Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells. Methods After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells. Results We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua. Conclusions In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

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Section: Resultsmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

Perfetto

Fan

Dahl

et al. 2015

J Assist Reprod Genet

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“…Prevalence of Th17/Th2 CD4+ cells in the decidua of successful pregnancy whereas of Th17 and Th17/Th1 cells in the decidua of unexplained recurrent abortion It has been reported that in "inevitable" spontaneous abortion with genital bleeding and in unexplained spontaneous abortion, the number of decidual Th17 cells increased compared to normal pregnancy [31,33]. Previously, we showed that in normal pregnancy both IL-17A, IL-17F and IL-22 are produced by decidua CD4+ T helper cells in association with IL-4.…”

Section: Associated Production Of Il-17 and Il-4 And Expression Of Thmentioning

confidence: 99%

Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce Interleukin-4

Lombardelli

Logiodice

Aguerre-Girr

et al. 2017

Journal of Reproductive Immunology

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Background: Trophoblast expressing paternal HLA-C antigens resemble a semiallograft, and could be rejected by maternal CD4+ T lymphocytes. We examined the possible role in human pregnancy of Th17 cells, known to be involved in allograft rejection and reported for this reason to be responsible for miscarriages. We also studied Th17/ Th1 and Th17/Th2 cells never investigated before. We defined for the first time the role of different Th17 subpopulations at the embryo implantation site and the role of HLA-G5, produced by the trophoblast/embryo, on Th17 cell differentiation. Methods:Cytokine production by CD4+ purified T cell and T clones from decidua of normal pregnancy, unexplained recurrent abortion, and ectopic pregnancy at both embryo implantation site and distant from that site were analyzed for protein and mRNA production. Antigen-specific T cell lines were derived in the presence and in the absence of HLA-G5. Results:We found an associated spontaneous production of IL-17A, IL-17F and IL-4 along with expression of CD161, CCR8 and CCR4 (Th2-and Th17-type markers) in fresh decidua CD4+ T cells during successful pregnancy. There was a prevalence of Th17/Th2 cells (producing IL-17A, IL-17F, IL-22 and IL-4) in the decidua of successful pregnancy, but the exclusive presence of Th17 (producing IL-17A, IL-17F, IL-22) and Th17/Th1 (producing IL-17A, IL-17F, IL-22 and IFN-γ) cells was found in the decidua of unexplained recurrent abortion. More importantly, we observed that Th17/Th2 cells were exclusively present at the embryo implantation site during tubal ectopic pregnancy, and that IL-4, GATA-3, IL-17A, ROR-C mRNA levels increased in tubal biopsies taken from embryo implantation sites, whereas Th17, Th17/Th1 and Th1 cells are exclusively present apart from implantation sites. Moreover, soluble HLA-G5 mediates the development of Th17/Th2 cells by increasing IL-4, IL-17A and IL-17F protein and mRNA production of CD4+ T helper cells. Conclusion:No pathogenic role of decidual Th17 cells during pregnancy was observed. Indeed, a beneficial role for these cells was observed when they also produced IL-4. HLA-G5 could be the key feature of the uterine microenvironment responsible for the development of Th17/Th2 cells, which seem to be crucial for successful embryo implantation.

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An insight into the role of the death receptor CD95 throughout pregnancy: Guardian, facilitator, or foe

Sagrillo-Fagundes¹,

Bienvenue-Pariseault²,

Legembre

et al. 2019

Birth Defects Research

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The prototype death receptor CD95 (Fas) and its ligand, CD95L (FasL), have been thoroughly studied due to their role in immune homeostasis and elimination of infected and transformed cells. The fact that CD95 is present in female reproductive cells and modulated during embryogenesis and pregnancy has raised interest in its role in immune tolerance to the fetoplacental unit. CD95 has been shown to be critical for proper embryonic formation and survival. Moreover, altered expression of CD95 or its ligand causes autoimmunity and has also been directly involved in recurrent pregnancy losses and pregnancy disorders. The objective of this review is to summarize studies that evaluate the mechanisms involved in the activation of CD95 to provide an updated global view of its effect on the regulation of the maternal immune system. Modulation of the CD95 system components may be the immune basis of several common pregnancy disorders.

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Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients

Cited by 321 publications

References 24 publications

Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce Interleukin-4

An insight into the role of the death receptor CD95 throughout pregnancy: Guardian, facilitator, or foe

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