Endoplasmic reticulum stress transmitted by endometrial stromal cells defines the fate of decidual dendritic cells toward tolerance or inflammation

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

San LUis

Congreso; Reunión Anual de la Sociedad Argentina de inmunología (SAI); 2023

123 (173) ENDOPLASMIC RETICULUM STRESS TRANSMITTED BYENDOMETRIAL STROMAL CELLS DEFINES THE FATE OF DECIDUALDENDRITIC CELLS TOWARD TOLERANCE OR INFLAMMATIONAna Schafir 1, Elizabeth Soczewski 1, Esteban Grasso 1, Laura Fernández 1, AlejandraGrassi Bassino 2, Jorgelina Blejer 2, Daiana Vota 1, Claudia Pérez Leirós 1, RosannaRamhorst 1 & Soledad Gori 1.1Laboratorio de Inmunofarmacología, IQUIBICEN-CONICET, Departamento de QuímicaBiológica, FCEN-UBA, Buenos Aires, Argentina, 2Fundación Hemocentro de Buenos Aires,Argentina.During the implantation window, endometrial stromal cells acquire a secretoryprofile associated with the expansion of its endoplasmic reticulum (ER), sufferinga physiological ER stress (ERS) and the consequent unfolded protein response(UPR). The signaling pathways involved in ERS/UPR are related with the onsetof a sterile inflammatory response that have a key role in endometrial receptivityand embryo implantation. We previously showed an altered ERS/UPR inendometria of women with reproductive complications. Considering that stromalcells condition maternal monocytes to a tolerogenic dendritic cell (DC) profile andERS can be cell-to-cell transmitted modulating immune profiles, here weevaluated the impact of ERS/UPR triggered on stromal cells on DCsdifferentiation and the involvement of ERS-transmission in their conditioning.Thus, human endometrial stromal cell line (HESC) was treated or not with apotent ERS-inducer Thapsigargin (Tg, an ER Ca2+ pump inhibitor) for 4h.Conditioned media (CM) were collected after 48h. Then, isolated monocytes fromperipheral blood mononuclear cells from healthy women were cultured withrhGM-CSF+rhIL-4 for 5 days in the absence/presence of CM.Monocyte-derived cultures differentiated with HESC+Tg CM showed a lowerfrequency of CD1a+CD14- compared with HESC CM (p