Lineage, maturity, and phenotype of uterine murine dendritic cells throughout gestation indicate a protective role in maintaining pregnancy

Dendritic cells (DCs) are known to play a major role in the induction, maintenance, and regulation of immune responses. Recently, DCs have been described to be present at the fetomaternal interface in human decidua. However, only limited information is available about DC presence, phenotype, and more importantly-function throughout gestation. Thus, we analyzed local (uterine) and systemic (blood) DCs in a murine model. DBA/2J mated C1BA/J females with vaginal plugs were separated and killed on Gestation Days (GDs) 1.5, 3.5, 5.5, 6.5, 7.5, 8.5, 10.5, 13.5, 15.5, or 17.5. Frequency of uterine and blood CD11c(+) DC, phenotype (coexpression of CD8alpha and major histocompatibility complex class II [MHC III antigens], and presence of intracellular cytokines (interieukins 12 and 10) were determined by flow cytometry. The morphology of DC in the pregnant uterus was evaluated by immunohistochernistry. In uterus, the relative number of CD11c(+) cells increased from CD 5.5, reaching a plateau on GD 9.5 until GD 17.5, while a transient peak of systemic CD11c(+) cells was found on GD 8.5 and 10.5. The vast majority of uterine DCs were CD8alpha(-) and thus, belonged to the myeloid lineage. interestingly, a significant peak of lymphoid DC was present on GD 1.5 and 5.5. Further, significantly more intracellular interieukin 10 than interleukin 12 was present in CD11c(+) cells. Interestingly, mature DCs (MHC II+) were diminished from GD 5.5 to 8.5. Characterization of CD11c(+) cell kinetics in uterus and blood reveals variation of phenotype during pregnancy, pointing toward an eminent immunoregulatory role of DCs throughout gestation at the fetomaternal interface.