Marilen Benner

B CELLS CONTRIBUTE TO DECIDUAL IMMUNITY 85 4 INTRODUCTION The uterus is a highly dynamic compartment. Each cycle, in preparation of pregnancy, the endometrium undergoes decidualization; a complex process of mucosal differentiation and influx of immune cells dictated by changing hormone levels. During the early stages of pregnancy, the well-timed presence of correctly functioning maternal immune cells contributing to both correct trophoblast invasion of semi-allogeneic fetal cells, and spiral artery remodeling, is essential (1- 4). Impairment in the recruitment, induction, or activation of immune components at the fetal- maternal interface can be harmful for mother and/or child. Depending on the nature and timing of the erroneous interactions, (recurrent) miscarriages, preeclampsia (PE), intra-uterine growth restriction or pre-term labor (PTL) may occur (3, 5, 6). After the initial challenge of implantation, the uterine immune environment faces the task of maintaining an anti-inflammatory state (3). Maternal uterine immune cells have to regulate the response to local or systemic infections, on the one hand counteracting threats to maternal and fetal health while on the other hand preventing a harmful inflammatory cascade. Any disbalance in the local immune response during this crucial window of development may affect the unborn child, with possible long-term effects on its immunity (7, 8) or cognitive function (9, 10). In the last stage of pregnancy, proinflammatory signaling, through infiltration of leucocytes into decidua and myometrium, and stimulation of cytokine secretion, facilitates physiologic uterine contractions (11). In addition, these adaptations may prepare for wound healing and tissue remodeling processes after parturition (12, 13). Although knowledge on the chronology of the systemic immune states during pregnancy has advanced in recent years, studies on gestational uterine immune cell fluxes are scarce (14, 15). Here, we examined local immune cell dynamics throughout human gestation using endometrial lymphocytes derived from menstrual blood alongside decidual tissue from 1 st and 2 nd trimester, and term decidua from uncomplicated pregnancies. We provide an overview of lymphocytes present within the uterus throughout gestation with a focus on B cells with IL-10 secreting capacities. RESULTS The uterus is a highly dynamic immune compartment Onset and maintenance of pregnancy elicits both short term, as well as long term adaptations of local immunity to facilitate healthy pregnancy. Thus, we assessed the immune cell composition in human uterine tissues (menstrual blood and decidua) from the non-pregnant phase, to 1 st and 2 nd trimester, up to term pregnancy by high dimensional immunophenotyping (Figure 1A). We first examined the abundance of the major lymphocyte cell types in the uterine mucosa