Marilen Benner

GENERAL INTRODUCTION AND SCOPE OF THIS THESIS 17 1 The factors on this list are of a diverse nature; and it is near impossible to give a full account of them. Still, we have to consider more than a single piece of the puzzle, with an open mind, if we wish to understand the bigger picture. AIM AND OUTLINE OF THIS THESIS In this thesis, we aim to introduce new perspectives on the regulation of uterine immunity. In Part I of this thesis, we explore the highly specialized local immune adaptations induced by pregnancy. We focus on tissue of the uterine mucosa. In Chapter 2 , we give an overview of the immune composition of the uterus. We examine how local immunity, especially NK and T cells of the endometrium, prior to implantation compare to the end of pregnancy. We dive deeper into the importance of specialized T cells in Chapter 3 , highlighting the presence of distinct types of regulatory T cells in human decidua. In reproductive immunology, most studies revolve around cell types of large abundance in the uterus. Even though small in numbers, we consider the possible contribution of B cells to the local immune interplay in Chapter 4 . To do so, we compare mucosal tissue of the non-pregnant uterus, during gestation, and upon delivery. We translate this knowledge on immune composition considering a broad spectrum of immune cells to patients suffering from recurrent miscarriages in Chapter 5 . In Part II , we examine yet another contributor of small abundance but possibly far-reaching impact: microbiota of the uterus. Due to their low biomass, uterine microbiota are difficult to detect. While presence of uterine microbiota is thus debated, microbes of the gut have shown how immunity cannot be fully understood without taking microbiota into account. We describe the possible contribution of microbes and their compounds on uterine immune cells in Chapter 6 . Manipulating the microbial balance by antibiotics during gestation might have an impact on the direct environment of the growing baby. In Chapter 7 we investigate if disrupting the natural microbial composition translates to immune adaptation during pregnancy. Finally, we summarize and discuss the findings of this thesis in Chapter 8 .