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1018 Myeloid cells in prgenancy and in inflammatory bowel disease: lessons from mouse models Ofer Fainaru, Gili Paz, Shay Hantisteanu, Mordechai Hallak, Yuval Ginsberg, Ron Beloosesky, Zeev Weiner RambamMedical Center, Haifa, NA, Israel, Assuta Medical Center, Tel Aviv, NA, Israel, Hillel Yaffe Medical Center, Hadera, NA, Israel, Hillel Yaffe Medcial Center, Hadera, NA, Israel OBJECTIVE: The inflammatory changes in the placenta that are intially associated with uterine quiescence but are later associated with labor and delivery need to be elucidated. During steady state, monocytes differentiate into macrophages that maintain tolerance and homeostasis. In inflammatory states, such as inflammatory bowel disease (IBD), this differentiation is arrested, the monocyte population increases and neutrophils accumulate. Additionally, these monocytes can differentiate into dendritic cells (DCs) capable of migrating into lymph nodes where thay can prime T cells and induce an immune response. We analyzed these alterations in placentas throughout normal pregnancy as compared to those observed in a mouse model of IBD. STUDY DESIGN: We utilized 6-8 week old CX3CR1-GFP mice (n1⁄425) in which the CD11b myeloid cell populations are defined as: CX3CR1 hi macrophages, CX3CR1 int pro-inflammatory effector monocytes, and CX3CR1 neg neutrophils. Under inflammatory conditions, these monocytes can give rise to CCR7-expressing CX3CR1 Ly6C DCs capable of migrating to the lymph nodes. We analyzed these cell populations by flow cytometry in single cell suspensions derived form placentas at designated time points in pregnancy (day 12,16,19). We compared these results to those observed in colons from and IBD model, in which mice are fed with dextran sulfate sodium salt, that induces severe inflammation. RESULTS: Surprisingly, throughout normal pregnancy a predominant pro-inflammatory effector monocyte population accumulates in the placenta (Figure 1). This corrleates to the acute inflammatory phase in IBD. Before labor and delivery the resting macrophage population disappears and an influx of neutrophils is demonstrated. We also detected that before delivery moonocyte derived DCs upregulate the chemokine receptor CCR7 indicating a transition from a "tolerant"to an "inflammatory” state from midpregnancy to term (Figure 2). CONCLUSION: The myeloid cell population in the placenta is unique demonstrating a high prepondrance of pro-inflammatory monocytes. This resembles an inflammatory state as observed in IBD and not a steady state. Before labor these monocytes do not differentiate into resting macrophages but rather into inflammatory effector DCs capable of migrtaion into lymph nodes and primng an immune response. These new findings may help shed new light on the cellular mechanisms underlying the sterile inflammation leading to labor and dleivery.