Laboratory of Reproductive and Mucosal Immunology
Our research group is based in the Department of Obstetrics and Gynecology of Wayne State University and the Perinatology Research Branch (PRB) of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) located on WSU's medical campus in Detroit, Michigan, USA.
Many common reproductive and developmental disorders have immunological basis. The study of the immunology of reproduction and development thus directs the understanding, treatment and prevention of these disorders. We seek to understand the regulation of systemic and mucosal immune responses during pregnancy, fetal and child development. Our goal is to harness the knowledge gained from our work to develop diagnostic, therapeutic and preventive strategies to reduce adverse pregnancy outcomes, infant mortality and disability.
Immunological concepts and technologies are integral to our scientific program. We adopt a comprehensive approach encompassing molecular, cellular, histological and immunological methods as well as the use of animal models and human samples.
B cells and antibodies during pregnancy
Antibodies constitute an important component of immune defense by promoting neutralization, opsonization, complement activation and by enhancing the immunoregulatory functions of various immune cells. In mucosal areas, antibodies confer frontline protection by limiting microbial invasion, eliciting immunity against noxious pathogens and promoting ignorance or tolerance to innocuous commensal microbes and food antigens. Dysregulation of antibody responses can cause a variety of pregnancy disorders. For example, impaired production of antibodies increases the susceptibility of the mother, the fetus and the newborn to infections. Conversely, uncontrolled production of antibodies against paternal fetal antigens and the ensuing inflammation are major risks of reproductive failure. We are studying the activation and antibody production of maternal B cells during pregnancy. We are also analyzing how mechanisms regulating the normal behaviors of B cells break down in pathological pregnancy, and whether the restoration of these mechanisms can alleviate or prevent diseases.
Immune tolerance mechanisms at the maternal-fetal interface
The placental immune system maintains an intricate balance of the various arms of immune responses for the successful reception and survival of an allogeneic fetus in the mother's uterus. A shift from this balance underlies many pregnancy disorders, such as preeclampsia, intrauterine growth restriction and preterm labor. Although it is known that many types of immune cells and molecules contribute to the placental immune environment, it is not well understood how such an environment is initiated or maintained. Using mouse models and human samples, we are identifying novel molecules and cells that play critical roles in the establishment and maintenance of the placental immune environment.
Fetal B cell development
Recent studies have suggested extensive crosstalk between the maternal and the fetal immune system and demonstrated that the fetal immune system also undergoes adaption in order for the fetus to successfully develop in the mother's uterus. The development of the fetal immune system has profound impact on postnatal health. We are focusing on fetal B cell hematopoiesis in syneneic and allogeneic mothers. Findings will contribute to the understanding of fetal hematopoiesis and help to identify strategies to promote the development of a healthier immune system of the newborn.
Mucosal immunity of the reproductive tract
The female reproductive mucosal immune system protects the host against infections and adapts to a spectrum of physiological events, such as menstruation and pregnancy. A major immune defense mechanism in the female genital tract is the production of mucosal antibodies, mainly class-switched IgA and IgG. A significant fraction of the antibodies in the genital tract secretion is produced locally by B cells residing in the genital mucosa. We are studying the hormonal and immunological regulation of genital antibody production in pregnant and non-pregnant states.
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