Endometrial stromal cells define the fate of decidual Dendritic Cells through endoplasmic reticulum stress transmission.

S GORI, A SCHAFIR, E SOCZEWSKI, E GRASSO, L FERNÁNDEZ, A GRASSI BASSINO, J BLEJER, D VOTA, C PÉREZ LEIRÓS, R RAMHORST

Chicago

Congreso; American Association of Immunologists; 2024

American Association of Immunologists

AAI registration: 4317Endometrial stromal cells define the fate of decidual Dendritic Cells through endoplasmic reticulum stress transmissionSoledad Gori 1, Ana Schafir 1, Elizabeth Soczewski 1, Esteban Grasso 1, Laura Fernández 1, Alejandra Grassi Bassino 2, Jorgelina Blejer 2, Daiana Vota 1, Claudia Pérez Leirós 1 & Rosanna Ramhorst 1 ..1Laboratorio de Inmunofarmacología, IQUIBICEN-CONICET, Departamento de Química Biológica, FCEN-UBA, Buenos Aires, Argentina, 2Fundación Hemocentro de Buenos Aires, Argentina.Endometrial stromal cells acquire a secretory profile associated with a physiological endoplasmic reticular stress (ERS) and related to the onset of a sterile inflammatory response to sustain embryo implantation. Here we evaluated the impact of endometrial stromal cells on Dendritic Cells (DC) differentiation through ERS-transmission. We used an in vitro model based on differentiated-monocytes from healthy women (with rhGM-CSF+rhIL-4) cultured in the absence/presence of Conditioned Media (CM) from stressed Human Endometrial Stromal Cells (HESC stimulated with Thapsigargin). Those monocyte-derived cultures differentiated with stressed-HESC showed a lower frequency of CD1a+CD14- accompanied by an increased CD86high cell-population and higher COX2 expression. We also detected an increase in IL-1β secretion and in AnnexinV+/PI+ cell-population, indicating a lytic programmed cell death. The ERS-transmission was confirmed by increased IRE1α expression on DC. In fact, IRE1α inhibitor prevented the conditioning to a pro-inflammatory DC profile. Finally, to investigate the impact of the DC-inflammatory profile on blastocyst implantation ability, we tested trophoblastic spheroids migration. Blastocyst-like spheroids displayed an altered trophoblast migration when were cultured with supernatant from stressed-DC. These results suggest that ERS might be transmitted from stromal cells to DC and its fine balance is required to maintain tolerance for successful embryo implantation and trophoblast migration.