IL-10-producing B cells play important role in the pathogenesis of recurrent pregnancy loss

Danaii, Shahla; Ghorbani, Farzaneh; Ahmadi, Majid; Abbaszadeh, Hossein; Koushaeian, Ladan; Soltani‐Zangbar, Mohammad Sadegh; Mehdizadeh, Amir; Hojjat‐Farsangi, Mohammad; Kafil, Hossein Samadi; Aghebati‐Maleki, Leili; Yousefi, Mehdi

doi:10.1016/j.intimp.2020.106806

Cited by 30 publications

(13 citation statements)

References 24 publications

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“…Previous studies have indicated that the reduced production of IL-10 may contribute to recurrent miscarriages ( 41 ). Patients with recurrent pregnancy loss exhibit a lower proportion of IL-10+ CD19+ B cells, and reduced levels of IL-10 in serum and supernatant of the stimulated B cell culture medium ( 42 ). The results of the current study are consistent with this, indicating that serum IL-10 was significantly lower in the missed abortion group.…”

Section: Discussionmentioning

confidence: 99%

The expression and clinical significance of three lncRNAs in patients with a missed abortion

et al. 2020

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Missed abortions are common complications that occur in early pregnancy, and impaired trophoblast functions have been indicated to be associated with their pathogenesis. The long noncoding RNAs (lncRNAs) Metastasis Associated Lung Adenocarcinoma Transcript 1 ( MALAT1) , HOX Transcript Antisense RNA ( HOTAIR) and Maternally expressed gene 3 ( MEG3) have been demonstrated to serve a crucial regulatory role in the mobility of trophoblast cells and embryo implantation. However, the expression profile and role of each of these three lncRNAs in patients with a missed abortion remain unclear. The expression of MALAT1 , HOTAIR , and MEG3 in decidual and villous tissues from 26 patient exhibiting a missed abortion and 26 healthy controls was detected using reverse-transcription quantitative PCR. Serum TNF-α, IL-1β, IL-6 and IL-10 levels were measured using ELISA, and serum estradiol and progesterone levels were measured with electrochemiluminescence immunoassays. Additionally, the correlations between lncRNA expression and the levels of cytokines and hormones were further analyzed. MALAT1 , HOTAIR and MEG3 expression was significantly higher in villous tissues of patients exhibiting a missed abortion compared with healthy controls. MALAT1 expression was higher in decidual tissues of patients exhibiting a missed abortion compared with healthy controls. Serum IL-10 levels were significantly lower in patients exhibiting a missed abortion compared with healthy controls. Serum estradiol and progesterone levels were significantly lower in the group of patients exhibiting a missed abortion compared with the control group. Furthermore, MALAT1 expression in villous tissue was inversely related to serum progesterone levels. The results of the current study suggest that MALAT1 may be associated with the pathogenesis of missed abortions.

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Section: Discussionmentioning

confidence: 99%

The expression and clinical significance of three lncRNAs in patients with a missed abortion

et al. 2020

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“…Th1/Th2 and Th17/Treg cell balance have an essential part in the establishment of a pregnancy‐favorable environment. During the peri‐implantation period, a controlled shift toward Th1 responses is involved in immune surveillance and avoids the excessive invasion of trophoblast 7,8 . After the placental implantation, making a shift toward Th2 is essential for the preservation and development of a normal embryo, the suppression of Th17 and Th1 cells by releasing interleukin (IL)‐13 and IL‐4, respectively, and an increase in allograft tolerance 8,9 .…”

Section: Lymphocytes and Pregnancymentioning

confidence: 99%

“…During the peri-implantation period, a controlled shift toward Th1 responses is involved in immune surveillance and avoids the excessive invasion of trophoblast. 7,8 After the placental implantation, making a shift toward Th2 is essential for the preservation and development of a normal embryo, the suppression of Th17 and Th1 cells by releasing interleukin (IL)-13 and IL-4, respectively, and an increase in allograft tolerance. 8,9 Additionally, Treg cells are the main factors for immunological tolerance, the acceptance of the fetus by the mother's immune system, and embryo implantation.…”

Section: Lymphoc Y Te S and Preg Nan C Ymentioning

confidence: 99%

T lymphocytes and preeclampsia: The potential role of T‐cell subsets and related MicroRNAs in the pathogenesis of preeclampsia

Zolfaghari

ArefNezhad

Parhizkar

et al. 2021

American J Rep Immunol

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Innate and adaptive immune systems have a crucial role in initiating and progressing some pregnancy disorders such as preeclampsia (PE), which is one of the pregnancy‐specific disorders that could result in neonatal and maternal morbidity and mortality. The dysregulation of the spiral artery and inadequate trophoblast invasion lead to PE symptoms through producing various inflammatory cytokines and anti‐angiogenic factors from the placenta. T lymphocytes play a special role in the epithelium and stroma of the human endometrium. CD4+ T helper (Th) cells, Th1/Th2, and Th17/T regulatory (Treg) balance mainly contribute to the establishment of a pregnancy‐favorable environment. This review examined the dysregulation of some cytokines produced from T cells, the dysregulation of the transcription factors of Th cells, the expression of chemokine receptors on T cells, as well as the effects of some factors including vitamin D on the activity of T cells, and finally, the dysregulation of various miRNAs related to T cells, which could cause PE.

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“…The female reproductive tract is also a mucosal system; however, B cells are comparatively understudied. Despite B-cell dysfunction being implicated in benign female reproductive pathologies, such as endometriosis, most studies are focused on peripheral B cells instead of endometrial B cells or relevant tissue B cells ( Gagné et al , 2003 ; Riccio et al , 2017 ; Danaii et al , 2020 ). As the innermost lining of the uterus, the human endometrium is a highly dynamic tissue that cyclically sheds and regenerates under the influence of steroid hormones throughout the menstrual cycle, in preparation for embryo implantation during the mid-luteal phase.…”

Section: Introductionmentioning

confidence: 99%

The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review

Shen

O’Donnell

Leon

et al. 2021

Human Reproduction Open

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STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute less than 5% of total endometrial CD45+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterised in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and in benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection, CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to ‘endometrium’, ‘B cells’ and B cell derivatives such as ‘antibody’ and ‘immunoglobulin’. Non-benign diseases were excluded using cancer related free-text terms, and searches were limited to English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as ‘Good’, ‘Fair’, or ‘Poor’ quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only ‘Good’ quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case-control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only “good” quality papers were included in this systematic review, there are variations in patients’ age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterisation of endometrial B cells and LAs could offer insights to endometrial B cell function, particularly in the context of autoimmune-associated pathologies such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interests to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915).

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IL-10-producing B cells play important role in the pathogenesis of recurrent pregnancy loss

Cited by 30 publications

References 24 publications

The expression and clinical significance of three lncRNAs in patients with a missed abortion

The expression and clinical significance of three lncRNAs in patients with a missed abortion

T lymphocytes and preeclampsia: The potential role of T‐cell subsets and related MicroRNAs in the pathogenesis of preeclampsia

The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review

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