What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Ozkan, Zehra Sema; Deveci, Derya; Şi̇mşek, Mehmet; Ilhan, Fulya; Rişvanlı, Ali; Sapmaz, Ekrem

doi:10.3109/14767058.2014.916676

Cited by 22 publications

(24 citation statements)

References 37 publications

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“…Women with a history of idiopathic recurrent pregnancy loss (RPL) showed lower levels of plasma IL‐35 in comparison to fertile women without a history of RPL. In addition, these women had a higher level of plasma IL‐17, which adversely affects the success of pregnancy and can be down‐regulated by IL‐35 . Although the fundamental mechanisms of IL‐35 function in reproduction are not clear, it has been confirmed that serum IL‐35 levels are elevated in normal pregnancy and correlate with increased estrogen and alpha‐fetoprotein (AFP) levels in early pregnancy.…”

Section: Resultsmentioning

confidence: 99%

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Regulatory B cells with IL‐35 and IL‐10 expression in a normal and abortion‐prone murine pregnancy model

Sławek

Lorek

Kędzierska

et al. 2019

American J Rep Immunol

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Determination of appropriate immunological interactions between the mother and the fetus and the establishment of immune tolerance are fundamental prerequisites for a successful pregnancy. Among them, the induction of a tolerogenic response to paternal antigens is considered necessary for the success of pregnancy. Disturbed immune tolerance can cause pregnancy disorders, such as spontaneous and recurrent miscarriages or preeclampsia. The crucial work of Aluvihare et al published in 2004 1 indicated for the first time that cell population with the CD4 + CD25 + phenotype played a leading role in maintaining pregnancy in mice. Following studies unambiguously confirmed that these were Treg cells characterized by the CD4 + CD25 + Foxp3 + phenotype. 2,3 It has been proven that in humans, there is an increase in Treg number during normal pregnancy and a decrease in their number and activity in spontaneous abortion cases. 3 It was also confirmed in the murine abortion-prone model of pregnancy (characterized by high rate of fetal resorption and Abstract Problem: Interleukin 35 is a relatively newly discovered cytokine that is produced by regulatory B cells (Bregs) and contributes to their suppressive function, which may contribute to fetal tolerance development and pregnancy maintenance. Therefore, the aim of this study was to determine the frequency of Bregs and expression of IL-35 and IL-10 in these cells in a normal and abortion-prone murine pregnancy model. Methods of study:The frequency of Bregs and expression level of IL-35 and IL-10 in these cells were measured in peripheral blood, uterine draining lymph nodes, uterus, and decidua using flow cytometry. The analysis was performed on days 3 and 14 of pregnancy in normal mice (CBA/JxBALB/c) and abortion-prone (CBA/JxDBA/2J) murine pregnancy model. Results: A decreased percentage of Breg cells expressing IL-35 on day 3 of pregnancyin the uterine draining lymph nodes and in peripheral blood in mice from the abortion group compared with the normal pregnancy group was observed. A similar decrease was also observed in the Breg cells population producing IL-10 in peripheral blood. In the uterus (3 dpc) and decidua (14 dpc), a lower percentage of CD19 + IL-35 + was also noted in the abortion-prone model. Conclusion:We indicated that the early stages of abortion-prone pregnancy (3 dpc) in mice were characterized by diminished frequency of B cells producing IL-35 at both local and peripheral levels. These results and the observed lower level of IL-35 in women suffering from recurrent spontaneous abortion suggest that IL-35 may be involved in the maintenance of pregnancy. K E Y W O R D Sabortion-prone, interleukin 35, maintenance of pregnancy, regulatory B cells

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Section: Resultsmentioning

confidence: 99%

“…However, studies on IL‐35 in human pregnancy and in reproduction field are limited. Thus far, IL‐35 levels have been studied mainly in the serum and trophoblasts of pregnant women or peritoneal fluid and endometrial tissue of women with endometriosis . In addition, IL‐35 was tested in the decidua of women after delivery.…”

Section: Resultsmentioning

confidence: 99%

Regulatory B cells with IL‐35 and IL‐10 expression in a normal and abortion‐prone murine pregnancy model

Sławek

Lorek

Kędzierska

et al. 2019

American J Rep Immunol

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“…Accordingly, IL‐35 is necessary for maintaining testicular immune privilege . Moreover, IL‐35 may also contribute to fetal–maternal tolerance during pregnancy …”

Section: Immune‐regulation and The Dilemma Of Treatment Of Chronic Inmentioning

confidence: 99%

“…Given the implication of immune-regulation in the development of maternal-fetal tolerance, lack of immuneregulation is considered as a newly suggested potential etiological cause of recurrent pregnancy losses (RPL). 77 Approximately 50% of RPL incidences are classified as idiopathic. 81 Accumulating data on dysregulation of immune tolerance in conjunction with RPLs might drive the discovering of new targets to prevent RPL.…”

Section: Il-35 An Immune-regulatory Marker In Pregnancymentioning

confidence: 99%

“…82,83 It was found that suppressor of cytokine signaling 3 (SOCS3) and IL-35 levels were significantly decreased in RPL cases compared to those in fertile control. 77 SOCS3 negatively regulates STAT3 activation in response to cytokines. This indicates that insufficient levels of SOCS3 and IL-35 might be associated with pregnancy loss due to an increased trophoblast responsiveness to cytokines and potentially appearance of a more inflammatory status.…”

Section: Il-35 An Immune-regulatory Marker In Pregnancymentioning

confidence: 99%

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IL‐35, a hallmark of immune‐regulation in cancer progression, chronic infections and inflammatory diseases

Teymouri

Pirro

Fallarino

et al. 2018

Intl Journal of Cancer

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Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target.

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Cytokines in the perinatal period – Part II

Chau

Markley

Juang

et al. 2016

International Journal of Obstetric Anesthesia

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What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Abstract: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.

Cited by 22 publications

References 37 publications

Regulatory B cells with IL‐35 and IL‐10 expression in a normal and abortion‐prone murine pregnancy model

Regulatory B cells with IL‐35 and IL‐10 expression in a normal and abortion‐prone murine pregnancy model

IL‐35, a hallmark of immune‐regulation in cancer progression, chronic infections and inflammatory diseases

Cytokines in the perinatal period – Part II

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