Exploration of Immunology

Special Issue Topic

Human Reproduction: Involvement of the Immune System

Guest Editors

Dr. Gérard Chaouat E-Mail

Emeritus of Hospital Saint Louis, Paris, France

Research Keywords: T cell, reproductive Immunology, placental suppression, NK cell

Dr. Satish Kumar Gupta E-Mail

ICMR Emeritus Scientist; Former J. C. Bose National Fellow; Former Deputy Director, National Institute of Immunology, Indian Council of Medical Research, Ramalingaswami Bhawan Ansari Nagar, New Delhi-110 029, India

Research Keywords: Reproductive Immunology/Biology, cell Biology, vaccine, immunodiagnosis

Dr. Nathalie Lédée E-Mail

Director of Medical Assisted Reproductive Services, Pierre Rouques Hospital, Paris, France

Research Keywords: Embryo implantation, oocytes, ICSI, implantation assisted reproductive techniques, embryo transfer

About the Special lssue

Prof. Gérard Chaouat, a leading figure in the field of immunology, was passed away on April 23, 2021, during editing this special issue. The subsequent work of this issue was managed by Dr. Satish Kumar Gupta & Dr. Nathalie Lédée.
We sincerely thank Prof. Chaouat for his efforts and strong support to our journal and this special issue. We will continue to keep this special issue on our journal website in honor of Prof. Gérard Chaouat.

From the Medawar paradox of "non rejection of the foetal allograft" by Sir Peter Medawar and early work of Freund on gamete autoimmunity, Immunology of Reproduction has massively evolved, with its failures (human anti HcG contraceptive vaccines) to present management of uterine cytokines allowing in Assisted Reproductive technology women with repeated implantation failures to obtain a greater success of pregnancy when they are properly treated than normal classical intercourse in healthy women. Among the conceptual revolutions is the fact that Natural Killer cells, viewed in the 80s as a threat to the foe to placental unit, which indeed can behave in pathological situations. As far as uterine NK cells are concerned, they are NECESSARY for successful pregnancy and secreting angiogenic factors. This issue will explore physiology and pathology of Human Reproduction, including pre-eclampsia which now is demonstrated to be a paternal specific immune deregulation of the "recognition" of the foe to placental unit. After a general introduction on the key steps of evolution of our concepts, totally unexpected in the 80s, we will examine each topic step by step.

We believe such a survey, which we will request to be as accessible as possible to foreigners to the field, will fascinate immunologists and remind them that surprisingly, as human primates, without the circuits we will describe, …. They would not be there, and that in this respect immunology now appears physiologically as important as endocrinology in reproduction.

Keywords: Immunity reproduction gametes, tolerance placenta, immunopathology

Published Articles

Open Access Review

Natural killer cell-mediated immunopathology in recurrent pregnancy losses

Natural killer (NK) cells have a dual role in human reproduction for maternal-fetal tolerance and protection from infection. During the ovarian cycle and pregnancy, peripheral NK (pNK) and uterine N

Published: October 30, 2022 Explor Immunol. 2022;2:693–722

DOI: https://doi.org/10.37349/ei.2022.00077

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Open Access Review

Do endometrial immune changes with age prior to menopause compromise fertility in women?

Menopause signals the end of the reproductive period in women. However, fertility and fecundity decrease with increasing age prior to menopause demonstrating that changes in the premenopausal female

Published: October 29, 2022 Explor Immunol. 2022;2:677–692

DOI: https://doi.org/10.37349/ei.2022.00076

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Open Access Review

A non-redundant role of complement protein C1q in normal and adverse pregnancy

Complement component 1q (C1q) is the recognition molecule of the classical pathway of the complement system that can bind to an array of closely spaced antigen-bound immunoglobulin G (IgG) and IgM a

Published: August 31, 2022 Explor Immunol. 2022;2:622–636

DOI: https://doi.org/10.37349/ei.2022.00072

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Open Access Review

Uterine natural killer cells and successful pregnancy: from mouse experiments to human physiology

Uterine natural killer (uNK) cells, a specific type of natural killer (NK) cells, are important cells at the foeto-maternal interface in humans as well as in mice. uNK cells are part of the innate l

Published: August 25, 2022 Explor Immunol. 2022;2:518–539

DOI: https://doi.org/10.37349/ei.2022.00065

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Open Access Review

Contribution of immunology to build precision medicine in reproduction: present and future

Infertility affects millions of people of reproductive age. The failure of a blastocyst to implant is a leading cause of psychological distress. It became increasingly evident that an effective immu

Published: August 26, 2022 Explor Immunol. 2022;2:558–571

DOI: https://doi.org/10.37349/ei.2022.00067

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Open Access Review

Pathogenesis of the obstetric antiphospholipid syndrome: the key role of beta 2 glycoprotein I

Antiphospholipid syndrome (APS) is defined by recurrent pregnancy morbidity and/or vascular thrombosis associated with the persistent presence of antibodies against anionic phospholipid-binding prot

Published: August 19, 2022 Explor Immunol. 2022;2:510–517

DOI: https://doi.org/10.37349/ei.2022.00064

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Open Access Review

Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation

Endometriosis (EMS) is an inflammatory, gynaecologic disease characterized by the growth of endometrial tissues outside the uterus. With no satisfactory therapies or non-invasive diagnostics availab

Published: July 26, 2022 Explor Immunol. 2022;2:454–483

DOI: https://doi.org/10.37349/ei.2022.00062

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Open Access Review

Cytokines and pregnancy complications: modulation for prevention and treatment

“There is many a slip twist the cup and the lip” is a proverb that dates back to the 3rd century. This proverb comes to mind while writing a review on pregnancy loss; so many complications can occur between fertilization and development of the embryo through the long period of gestation until successful delivery of the baby. These include failure of implantation of the embryo, spontaneous miscarriage in the first trimester, pre-eclampsia in the second trimester, premature rupture of fetal membranes, pre-term labour, and pre-term delivery. The maternal immune system which does a phenomenal job of protecting the host from a daunting variety of infections, sometimes also mounts adverse reactions that complicate pregnancy and endanger the fetus. Maternal immune reactions that can adversely affect pregnancy have been shown to be mediated by lymphocytes, macrophages and natural killer cells, and by cytokines secreted by these cellular effectors. This review summarizes the deleterious effects of cytokines leading to recurrent spontaneous miscarriage, pre-eclampsia and pre-term delivery, which are the major complications of pregnancy. It then goes on to discuss the potential use of progesterone and dydrogesterone, an orally-administered progestogen, as immunomodulatory molecules that can be considered for the prevention and/or treatment of these complications.

Published: June 27, 2022 Explor Immunol. 2022;2:414–427

DOI: https://doi.org/10.37349/ei.2022.00059

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Open Access Review

Polycystic ovary syndrome and immune deregulation: what do hormones want to say?

Polycystic ovary syndrome (PCOS) is one of the most frequently observed endocrinopathies among women of reproductive age that redound to subfertility. The specific etiology of this heterogenic syndr

Published: June 27, 2022 Explor Immunol. 2022;2:393–413

DOI: https://doi.org/10.37349/ei.2022.00058

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Open Access Review

Inviting regulatory T cells to pregnant endometrium: friends or foes in adverse pregnancy outcomes?

Among decidual immune cells, regulatory T cells (Tregs) have been unanimously recognized as central contributors to tolerance and maintenance of healthy pregnancy. Numerical and functional downregul

Published: June 13, 2022 Explor Immunol. 2022;2:363–382

DOI: https://doi.org/10.37349/ei.2022.00056

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Open Access Review

The influence of reproductive hormones on systemic lupus erythematosus

Humans are afflicted by a wide spectrum of autoimmune disorders, ranging from those affecting just one or a few organs to those associated with more systemic effects. In most instances, the etiology

Published: June 07, 2022 Explor Immunol. 2022;2:351–362

DOI: https://doi.org/10.37349/ei.2022.00055

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Open Access Perspective

Endometriosis and autoimmunity

Endometriosis is an inflammatory oestrogen-dependent chronic disease and is mainly expressed by pain and increased infertility. Several studies showed an increased prevalence of autoimmune systemic

Published: February 16, 2022 Explor Immunol. 2022;2:25–31

DOI: https://doi.org/10.37349/ei.2022.00034

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Open Access Review

Pregnancy depends on a delicate balance of immune activation and regulation

It is well recognized that immune tolerance is important to prevent semiallografted fetuses from rejection by maternal immunocompetent cells; however, immune activation also plays an important role

Published: December 31, 2021 Explor Immunol. 2021;1:461–478

DOI: https://doi.org/10.37349/ei.2021.00031

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Open Access Review

Progesterone induced blocking factor in health and disease

The foetus expressing paternal antigens ought to be “rejected” by the maternal immune system. However, the immunological relationship of the mother and the foetus does not follow the rules of transplantation immunology. Maternal immune functions are re-adjusted during pregnancy, to create a tolerant environment for the developing foetus. Progesterone and its downstream mediator; the progesterone induced blocking factor (PIBF) are important in this process. The mRNA transcribed from the PIBF1 gene contains 18 exons, and codes for a 90 kDa protein. The 90 kDa form is associated with the centrosome and plays a role in cell cycle regulation, while smaller isoforms produced by alternative spicing are secreted, and bind to the glycosylphosphatidylinositol (GPI) anchored PIBF receptor. Upon ligation, the former forms a heterodimer with the alpha chain of the interleukin-4 (IL-4) receptor and activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, via which, PIBF induces increased production of T helper2 (Th2) cytokines. PIBF regulates natural killer (NK) cytotoxicity, by inhibiting perforin release from the cytoplasmic granules of NK cells. During normal human pregnancy, the serum concentrations of PIBF increase with gestational age, and lower than normal serum levels predict spontaneous pregnancy termination. Depletion of PIBF during the peri-implantation period in mice, results in lower implantation and increased resorption rates, together with increased decidual and peripheral NK activity, downregulation of the genes implicated in T cell activation in CD4+ cells, and Th1 differentiation of the T cells. PIBF is expressed in rapidly proliferating immature cells as well as several tumours, and regulates invasion. The PIBF gene has been identified in the chromosomal region 13q21-q22—which is a common site for somatic deletions in a variety of malignant tumours. These data suggest that PIBF might be involved in tumorigenesis

Published: December 31, 2021 Explor Immunol. 2021;1:406–417

DOI: https://doi.org/10.37349/ei.2021.00027

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Open Access Review

A unique vaccine for birth control and treatment of advanced stage cancers secreting ectopically human chorionic gonadotropin

This article is a tribute and homage to Gerard Chaouat who invited me to contribute this article. My years in France have remained very memorable to me. Reviewed briefly is the vaccine that was made

Published: December 31, 2021 Explor Immunol. 2021;1:398–405

DOI: https://doi.org/10.37349/ei.2021.00026

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Open Access Review

Preeclampsia—an immune disease? An epidemiologic narrative

The maternal syndrome preeclampsia is triggered by syncytiotrophoblast (STB) stress; the heterogeneity of the syndrome is caused by the different pathways leading to this STB stress. Inflammation pl

Published: December 31, 2021 Explor Immunol. 2021;1:325–340

DOI: https://doi.org/10.37349/ei.2021.00022

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Open Access Review

Immunoregulation in the testis and its implication in fertility and infections

The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm anti

Published: December 31, 2021 Explor Immunol. 2021;1:309–324

DOI: https://doi.org/10.37349/ei.2021.00021

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