Effects of treatment with hydroxychloroquine on the modulation of Th17/Treg ratio and pregnancy outcomes in women with recurrent implantation failure: clinical trial

Sadeghpour, Sonia; Berenji, Morteza Ghasemnejad; Nazarian, Hamid; Ghasemnejad, Tohid; Nematollahi, Mohammad Hadi; Abroon, Sina; Paktinat, Shahrokh; Khoei, Heidar Heidari; Berenji, Hojjat Ghasemnejad; Novin, Marefat Ghaffari

doi:10.1080/08923973.2020.1835951

Cited by 18 publications

(11 citation statements)

References 33 publications

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“…They are characterized as cells that preferentially produce interleukins, including IL-17A, IL-17F, IL-21, and IL-22. RORγt, the steroid receptor–type nuclear receptor, induces the development of Th17 cells and production of IL-17, which are commonly used to identify Th17 cells, along with specific cytokines (IL-17 and IL-21) [ 38 , 39 , 40 , 41 ]. Treg cells are known to inhibit immune responses by producing the anti-inflammatory cytokines, IL-10 and TGF-β.…”

Section: Discussionmentioning

confidence: 99%

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Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance

Fan

Sha

et al. 2021

Journal of Reproduction and Development

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Immune imbalance of Treg/Th17 cells may contribute to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF-ET). In this study, we sought to determine the effect of intrauterine administration of mouse PBMCs prior to embryo implantation on endometrial receptivity and embryo implantation, and examine the underlying mechanism of Treg/Th17 cell balance following intrauterine administration of PBMCs. Pregnant mice were randomly divided into three groups: control group, embryo implantation dysfunction (EID) group, and EID with PBMCs group, and the number of embryo implantation sites was recorded during early pregnancy (Pd7.5). The balance of Treg/Th17 cells in the peripheral blood, spleen, and local implantation sites was detected during the peri-implantation period (Pd4.0) and early pregnancy (Pd7.5). The EID group demonstrated a significant decrease in the number of embryo implantation sites, while the EID with PBMCs group demonstrated higher number of embryo implantation sites compared to the EID group. The balance of Treg/Th17 cells in the peripheral blood and spleen tissues was not significantly different between the aforementioned groups. However, the local uterine ratio of the Treg/Th17 cells increased in the EID with PBMCs group compared to that in the EID group. Collectively, we found that intrauterine administration of PBMCs prior to embryo implantation effectively promotes embryo implantation rates. This may be attributed to the improvement in the local immune balance of Treg and Th17 cells compared with the overall immune balance.

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Section: Discussionmentioning

confidence: 99%

“…However, Sadeghpour et al . found that when local Th17 cells decreased and Treg cells increased, the pregnancy rate in patients with RIF did not improve significantly [ 41 ]. This is not entirely consistent with the findings of Ahmadi et al .…”

Section: Discussionmentioning

confidence: 99%

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance

Fan

Sha

et al. 2021

Journal of Reproduction and Development

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“…The Th17/Treg ratio is associated with pregnancy outcomes such as recurrent implantation failure (96). However, recent research in recurrent implantation failure has shown that the Th17/Treg ratio was susceptible to Treg enhancement and Th17 diminishment using hydroxychloroquine treatment but the pregnancy outcomes were not significantly improved (97). In addition, Breg, the subpopulation of the CD19+CD24hiCD27+ phenotype, were expanded by producing IL-10.…”

Section: The Mother-baby Immune Trafficking: Fetal Immature Antigens and Maternal Immune Inertness?mentioning

confidence: 99%

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

2021

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Maternal-fetal immune-tolerance occurs throughout the whole gestational trimester, thus a mother can accept a genetically distinct fetus without immunological aggressive behavior. HLA-G, one of the non-classical HLA class I molecules, is restricted-expression at extravillous trophoblast. It can concordantly interact with various kinds of receptors mounted on maternally immune cells residing in the uterus (e.g. CD4+ T cells, CD8+ T cells, natural killer cells, macrophages, and dendritic cells) for maintaining immune homeostasis of the maternal-fetus interface. HLA-G is widely regarded as the pivotal protective factor for successful pregnancies. In the past 20 years, researches associated with HLA-G have been continually published. Indeed, HLA-G plays a mysterious role in the mechanism of maternal-fetal immune-tolerance. It can also be ectopically expressed on tumor cells, infected sites and other pathologic microenvironments to confer a significant local tolerance. Understanding the characteristics of HLA-G in immunologic tolerance is not only beneficial for pathological pregnancy, but also helpful to the therapy of other immune-related diseases, such as organ transplant rejection, tumor migration, and autoimmune disease. In this review, we describe the biological properties of HLA-G, then summarize our understanding of the mechanisms of fetomaternal immunologic tolerance and the difference from transplant tolerance. Furthermore, we will discuss how HLA-G contributes to the tolerogenic microenvironment during pregnancy. Finally, we hope to find some new aspects of HLA-G in fundamental research or clinical application for the future.

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“…It has also been demonstrated that daily administration of hydroxychloroquine (HCQ) in RIF women downregulated Th17 cytokines and additionally upregulated Treg cytokines. Both of these processes, through influencing the Th17/Treg ratio, compensate for the immune response [ 110 ].…”

Section: Treatment Of Rifmentioning

confidence: 99%

Biomolecular Markers of Recurrent Implantation Failure—A Review

Mrozikiewicz

Ożarowski

Jȩdrzejczak

2021

IJMS

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Currently, infertility affects 8–12% of reproductive age couples worldwide, a problem that also affects women suffering from recurrent implantation failure (RIF). RIF is a complex condition resulting from many physiological and molecular mechanisms involving dynamic endometrium–blastocyst interaction. The most important are the endometrial receptivity process, decidualization, trophoblast invasion, and blastocyst nesting. Although the exact multifactorial pathogenesis of RIF remains unclear, many studies have suggested the association between hormone level imbalance, disturbances of angiogenic and immunomodulatory factors, certain genetic polymorphisms, and occurrence of RIF. These studies were performed in quite small groups. Additionally, the results are inconsistent between ethnicities. The present review briefly summarizes the importance of factors involved in RIF development that could also serve as diagnostic determinants. Moreover, our review could constitute part of a new platform for discovery of novel diagnostic and therapeutic solutions for RIF.

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Effects of treatment with hydroxychloroquine on the modulation of Th17/Treg ratio and pregnancy outcomes in women with recurrent implantation failure: clinical trial

Cited by 18 publications

References 33 publications

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

Biomolecular Markers of Recurrent Implantation Failure—A Review

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