Role of decidual CD14(+) macrophages in the homeostasis of maternal-fetal interface and the differentiation capacity of the cells during pregnancy and parturition.

OBJECTIVE: Decidual macrophages (dMΦs) have been implicated in fetal tolerance, but little information is known regarding their differentiation capacity and interactions with T cells. The present study aimed to investigate the immunological characteristics of dMΦs at mid and term pregnancy. METHODS: The dMΦs were analyzed for their phenotypes and cytokine production by flow cytometry and ELISA, respectively. The transendothelial trafficking model was implemented to allow the dMΦs to differentiate. The differentiated cells from dMΦs were also measured for their phenotypes and cytokine production with same methods. The capacity of dMΦs or the differentiated cells from dMΦs to stimulate allogeneic T lymphocyte proliferation was evaluated by T lymphocyte stimulation assays. T cell differentiation was determined by flow cytometry. RESULTS: The dMΦs in the mid-pregnancy (Mid-dMΦs) resembled the M2 phenotype. The differentiated cells from Mid-dMΦs had little stimulatory capacity on T cell proliferation and favored regulatory T cell differentiation. The dMΦs at term differentiated into dendritic (DC)-like cells, stimulating T cell activation, proliferation, and differentiation into IFN-γ-producing T cellsdecidual CONCLUSIONS: The present study suggests that the differences in phenotypes and cytokine production between Mid- and Term-dMΦs relate to their different roles in the homeostasis of the maternal-fetal interface. Mid-dMΦs differentiate into DC-like cells with immunosuppressive properties, playing an important role in maintaining homeostasis required for a successful pregnancy. Term-dMΦs differentiate into DC-like cells with immunostimulatory properties, likely involved in the activation of labor. The different differentiation capacities of dMΦs in the varied pregnancy stages may be due to the placental microenvironment.

Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model.

Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.