Regulatory interactions between DC and NK cells are not bidirectional during mouse implantation.

BARRIENTOS, G; TIRADO-GONZÁLEZ, I; FRANK, P; ARCK, PC; KLAPP, BF; BLOIS, SM

Congreso; XI International Congress of Reproductive Immunology; 2010

Uterine DC and NK cells appear to play a crucial role during early pregnancy regulating maternal immunity as well as decidual growth and neovascularization. However, complex regulatory interactions between DC and NK cells hinder the assessment of their specific functions within the decidual milieu.Objectives: To characterize the cross-talk between DC and NK cells in the decidua and investigate its relevance during the implantation process in mice. Methods: We used a transgenic mouse model which allows to deplete DC in vivo, and the asialo GM1 antibody strategy for ablation of NK cells to investigate the specific functions of these subsets during embryo implantation,. Uterine tissue at gestation days 5.5 and 7.5 was analysed by RT-PCR and IHC for the expression of IL-11 and the cell cycle regulators cyclin D3, p21 and cyclin E at Gd 5.5 and 7.5 as hallmarks of stromal cell proliferation, differentiation and poliploidization. Decidual vascular development and remodeling was assessed based on the expression of PECAM-1, alpha smooth muscle actin and the VEGF/VEGFR system mediating angiogenesis. Results: Even though uterine arterial remodeling was impaired, the individual depletion of NK cells did not affect stromal cell proliferation and differentiation. In contrast, the combined depletion of DC and NK cells led to severe impairments on decidual differentiation, reduced vascularization and angiogenic activity at the implantation sites similar to those described upon DC depletion.Conclusions: NK cells promote vascular modifications to support normal decidual development, but do not seem to directly affect stromal cell proliferation and differentiation. These functions are nevertheless insufficient to prevent implantation failure in the absence of DC, highlighting a hierarchical relationship in which  NK cells are subordinate to the actions of DC driving embryo implantation