EXACERBATED ENDOPLASMIC RETICULUM STRESS SUFFERED BY ENDOMETRIAL STROMAL CELLS ALTERS THE CONDITIONING OF MATERNAL MONOCYTES TO A TOLEROGENIC DENDRITIC CELL PROFILE

SCHAFIR A; FERNÁNDEZ L; SOCZEWSKI E; VOTA D; BESTACH Y; CASTAGNOLA L; BLEJER J; GRASSI BASSINO A; PÉREZ LEIRÓS C; GORI S; RAMHORST R

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2021

Endometrial stromal cells undergo physiological endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) allowing the secretion of immunoregulators and associated with a sterile inflammatory response to achieve a successful implantation. However, an exacerbated ERS/UPR was found in endometria of women with recurrent pregnancy loss, suggesting that a rigorous balance is required. Considering that stromal cells condition maternal monocytes to a tolerogenic dendritic cell profile, here we evaluated the impact of ERS/UPR triggered on stromal cells on monocyte differentiation. Thus, human endometrial stromal cell line (HESC) were treated: +/- Thapsigargin (an ERS-inducer Tg, 4h) or +/- decidualization stimuli (MPA+db-cAMP for 8 days). Conditioned media (CM) were collected after 48h. Then, isolated monocytes from peripheral blood mononuclear cells from healthy women were cultured with rhGM-CSF+rhIL-4 for 5 days in the absence/presence of CM. Monocyte-derived cultures differentiated with HESC+Tg CM showed a lower frequency of CD1a+CD14- cells compared with HESC CM, quantified by FACS analysis (p