TY - JOUR KW - decidua KW - extracellular vesicles KW - Inflammation KW - interferon epsilon KW - Oxidative Stress KW - vaginal epithelial cells AU - Emmanuel Amabebe AU - Lauren S. Richardson AU - Awanit Kumar AU - Ramkumar Menon AU - Brandie D. Taylor AB - Problem We tested the hypothesis that oxidative stress (OS)-induced inflammatory response in decidual cells (DECs) may transfer and/or trigger the release of interferon epsilon (IFNε)-positive extracellular vesicles (EVs) from vaginal epithelial cells (VECs) to minimize vaginal disturbances. Method of Study VECs were treated for 48 h under the following conditions: (1) standard VEC media, (2) OS-inducing cigarette smoke extract (CSE); and supernatant from (3) normal/untreated DECs, and (4) CSE-treated DECs. The concentration of cytoplasmic, secreted, and VEC-derived EV bound IFNε (n = 3 each) was measured by enzyme-linked immunosorbent assay (ELISA). EVs were isolated from culture media by cushioned-density gradient ultracentrifugation and characterized by immunoblotting and nanoparticle tracking analysis. Results Induction of OS in VECs with CSE increased intracellular IFNε in VECs (p = 0.0007) but not free or EV-bound IFNε compared to control VECs. Exposure to conditioned media from untreated and CSE-treated DECs induced increased intracellular (p = 0.004, p = 0.049) and free IFNε (p = 0.04, p = 0.03) from VECs. VEC-derived EVs (126 ± 11.8 nm) expressed exosome markers, and did not change in size regardless of the treatment but decreased in number due to exposure to untreated (p = 0.004) and CSE-treated DECs (p = 0.025) conditioned media. Furthermore, VEC exosomal IFNε increased by 2.6-fold (p = 0.0001, untreated DECs) and ∼4-fold (p = 0.041, CSE-treated DECs) compared to controls. Conclusions Mucosal immune defense mediated by IFNε may be an innate response by VECs under OS. This was further evidenced by an overall increase in IFNε due to both physiologic and pathologic impact of decidua on VECs. IFNε may indicate a stress response by VECs or paracrine crosstalk between gestational tissues. BT - American Journal of Reproductive Immunology DA - 2025 DO - 10.1111/aji.70129 IS - 3 LA - en N2 - Problem We tested the hypothesis that oxidative stress (OS)-induced inflammatory response in decidual cells (DECs) may transfer and/or trigger the release of interferon epsilon (IFNε)-positive extracellular vesicles (EVs) from vaginal epithelial cells (VECs) to minimize vaginal disturbances. Method of Study VECs were treated for 48 h under the following conditions: (1) standard VEC media, (2) OS-inducing cigarette smoke extract (CSE); and supernatant from (3) normal/untreated DECs, and (4) CSE-treated DECs. The concentration of cytoplasmic, secreted, and VEC-derived EV bound IFNε (n = 3 each) was measured by enzyme-linked immunosorbent assay (ELISA). EVs were isolated from culture media by cushioned-density gradient ultracentrifugation and characterized by immunoblotting and nanoparticle tracking analysis. Results Induction of OS in VECs with CSE increased intracellular IFNε in VECs (p = 0.0007) but not free or EV-bound IFNε compared to control VECs. Exposure to conditioned media from untreated and CSE-treated DECs induced increased intracellular (p = 0.004, p = 0.049) and free IFNε (p = 0.04, p = 0.03) from VECs. VEC-derived EVs (126 ± 11.8 nm) expressed exosome markers, and did not change in size regardless of the treatment but decreased in number due to exposure to untreated (p = 0.004) and CSE-treated DECs (p = 0.025) conditioned media. Furthermore, VEC exosomal IFNε increased by 2.6-fold (p = 0.0001, untreated DECs) and ∼4-fold (p = 0.041, CSE-treated DECs) compared to controls. Conclusions Mucosal immune defense mediated by IFNε may be an innate response by VECs under OS. This was further evidenced by an overall increase in IFNε due to both physiologic and pathologic impact of decidua on VECs. IFNε may indicate a stress response by VECs or paracrine crosstalk between gestational tissues. PY - 2025 EP - e70129 T2 - American Journal of Reproductive Immunology TI - Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/aji.70129 VL - 94 Y2 - 2025-09-17 SN - 1600-0897 ER -