INDUCTION OF THE TOLEROGENIC DENDRITIC CELLS DC-10 INTO THE DECIDUA: THE CONTRIBUTION OF TROPHOBLAST CELLS

ANA SCHAFIR; LAURA FERNÁNDEZ; ESTEBAN GRASSO; SOLEDAD GORI; VANESA HAUK; JORGELINA BLEJER; CLAUDIA PÉREZ LEIRÓS; BRENDA LARA; ALEJANDRA GRASSI BASSINO; ROSANNA RAMHORST

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SAIC, SAIC, SAFIS

Immunomodulation and tolerance induction are strictly required during pregnancy. A novel and distinctive subset of HLA-G+ tolerogenic dendritic cell, DC-10, was found increased in first-trimester decidua. Recently, we showed that decidualized cells can conditionmaternal monocytes to DC-10 profile during the pre-implantation period. Here we aimed to explore the potential contribution of DC-10 in first-trimester decidua and the impact of trophoblast cells in its induction. First, we performed an integrated bioinformatic analysis since public array-based data. We found 212 up-regulated genes in DC-10 relative to mature and immature DC (p<0.05) and a significant enrichment of this specific genes in first-trimester decidua CD14+ cells (FDR<0.25). Interestingly, at least 10 genes are associated with characteristic processes related to pregnancy such as decidualization, implantation, and placentation, suggesting a potential role of DC-10 in these processes. Then, we evaluated the contribution of first-trimester trophoblast cells to the induction of decidual DC-10. Thus, isolated monocytes from blood of healthy women were cultured with rhGM-CSF+rhIL-4 for 5 days in the absence/presence of conditioned media (CM) of human first-trimester extravillous trophoblast cell line (HTR8). We observed that HTR8-CM inhibited the differentiation to the CD1a+ immature DC (p<0.05, Wilcoxon test) and induced the maintenance of CD14 on monocyte-derived cells, a marker of tolerogenic DC. Also, a significant increase of CD83+CD86low subset was observed in HTR8-CM culture, accompanied by a higher production of IL-1β, a key implantation mediator (p<0.05). Notably, after HTR8-CM cultures, DC displayed a higher expression of tolerogenic markers associated to DC-10 profile, IL10 and HLA-G (p<0.05). The present results suggest that trophoblast cells contribute to the induction of DC-10, whose may play a key role in different processes related to embryo implantation and pregnancy maintenance.