Since the birth of Reproductive Immunology when Peter Medawar first posed the question of why the semi-allogeneic fetus is not rejected by the mother, scientists have been intrigued by the role of the immune system in pregnancy. In 1981, the American Society of Reproductive Immunology was founded, and over the past 30 years, it has seen the field flourish and expand to encompass a wide range of topics. We now know that the immune system and immunological processes are involved in more than just fetal immunotolerance, by playing a role in maintaining host protection throughout the non-pregnant genital tract; preparing the endometrium for implantation of the blastocyst; and supporting both pregnancy and parturition. Moreover, disruptions in these well-controlled immune functions can play important contributory roles in infectious diseases, infertility, and a number of pregnancy complications. By understanding the basic immunological mechanisms in reproduction, only then can we begin to determine better ways to predict and prevent infertility, obstetrical problems, and women’s health issues. The aim of this special issue is to highlight some of the key areas of human Reproductive Immunology research as up-to-date reviews by leaders in the field.
This special issue begins with two overviews of the interactions between the immune system and reproduction. Dr Yoshinaga presents an overview on the role of immunological factors in pregnancy. He defines the role of blastocyst implantation factors as immunological products regulating the process of implantation and reproduction. Dr Mor and Cardenas discuss what are the potential interactions between the maternal and fetal immune systems in normal pregnancy.
The next section presents four reviews on the role of immune cells during implantation and pregnancy. Dr Mandelboim provides the first review on how the unique properties of uterine NK cells facilitate the establishment of pregnancy and discusses their origins. Dr Zenclussen and colleagues assess the role of T regulatory cells in promoting immune tolerance against the fetus. Drs Nagamatsu and Schust give an in-depth overview of the phenotype and functions of decidual macrophages throughout gestation and discuss their roles in certain pregnancy disorders. Finally, Dr Croy and her team talk about how studies in mice are helping to answer questions regarding the role of NK cells at the maternal–fetal interface in vasoregulation and angiogenesis.
In the next section, cytokines and other regulatory factors in pregnancy, Jessica Thaxton and Surendra Sharma discuss the immunomodulatory properties of IL-10 and its importance in pregnancy. Udo Markert and colleagues give an overview of the role of cytokines, MMPs, and galectins in the regulation of trophoblast invasion.
We next present three reviews on immunotolerance in pregnancy, which begins with Drs Petroff and Perchellet describing how placental B7 family members regulate T-cell responses generated toward the fetus. Dr Mincheva-Nilsson and colleagues give a highly detailed overview of the characteristics of placental-derived exosomes and their role in regulating the maternal immune system during pregnancy. Lastly, Dr. Redman describes the role of placental-derived material, as well as other immunological mechanisms, in the pathogenesis of preeclampsia.
The next section is on sexually transmitted infections and inflammation. Dr Wira and colleagues present an extremely detailed review on the role of steroid sex hormones in regulating the innate mucosal immunity of the non-pregnant female genital tract and how disruptions in natural antimicrobial production may render women vunerable to sexually transmitted infections. Dr Kaushic and her group discuss the ability of the female reproductive tract to generate specific anti-HIV responses. Alison Carey and Kenneth Beagley assess the impact Chlamydia trachomatis infection of the female reproductive tract has on women’s health and what methods are being employed in vaccine development.
In the final section of this special issue, clinical aspects of reproductive immunology, Drs Koga and Mor discuss in detail the role of Toll-like receptors in normal pregnancy as well as in pregnancy complications. The review presents potential clinical applications as a result of our understanding of Toll-like receptor biology. Dr Saito’s review discusses up-to-date information on T cells and pregnancy and their clinical association with pregnancy complications, such as preeclampsia and preterm labor. Similarly, Dr Kwak-Kim and colleagues give a clinical overview of how research on reproductive immunology may be applicable for clinical practice.
We conclude this special issue with an historical overview of the field of Reproductive Immunology by Dr Gerard Chaouat. His provocative discussion challenges old and new concepts and invite for novel approaches to understand this complex but relevant subject that is the immunology of pregnancy.
I thank all the authors involved in celebrating the field of Reproductive Immunology through their outstanding contributions.