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RANKL promotes and maintains decidualization of human endometrial stromal cells triggered by PGE2
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Abstracts / Journal of Reproductive Immunology 115 (2016) 71–90
as controls. On gestation day (gd) 15.5 and 18.5, fetal lung development was assessed histologically and the mRNA expression of regulatory proteins and differentiation markers was quantified by quantitative polymerase chain reaction. Stress challenge did not profoundly affect fetal lung development in male fetuses. However, female stress-challenged fetuses displayed less extensive terminal sac areas surrounded by thicker mesenchyme together with lower expression of insulin- like growth factor 1 receptor and surfactant protein-A than female control fetuses. Taken together, these findings suggest that prenatal stress induces a developmental delay of the lungs, evidenced by impaired branching, mesenchymal reduction and alveolarization in a sex-specific manner. This impaired lung development may increase the risk for airway diseases later in life, especially in the female offspring.
IL-11, prostaglandin E2 (PGE2) are involved in this process, the molecular mechanisms of it are not well understood. Here we found the expression of nuclear factor-kappaB receptor/nuclear factor-kappaB ligand (RANK/RANKL) in endometrial stromal cells (ESCs) was significantly lower than that in decidual stromal cells (DSCs). Compared to estrogen plus progesterone and cAMP, PGE2 obviously up-regulated the expression of member RANKL (mRANKL) and RANK on the surface of decidualized ESCs models in vitro, and this effect could inhibited by anti-human IL-1, IL-11 or IL-15 neutralizing antibody. In addition, mRANKL accelerated the process of decidualization in ESCs induced by PGE2 and up-regulated CD82 expression in DSCs, but not ESCs during decidualization. These results suggest that RANKL can stimulate decidualization of ESC derived by PGE2 and maintain the decidualization status of DSCs.
http://dx.doi.org/10.1016/j.jri.2016.04.268 P2-50 Presence and functionality of resident memory CD8 T cells in the pregnant mouse uterus Emiel D. Post Uiterweer, Johan Siewiera, Patrice Nancy, Adrian Erlebacher Department of Pathology, NYU School of Medicine, New York City, NY, USA Resident memory T cells (Trm), a newly described T cell subset, possess a robust ability to induce local inflammation and lymphocyte recruitment, thus raising questions about their potential impact on pregnancy success if present and active within the pregnant uterus. Here, we studied the behavior of ovalbuminspecific uterine CD8+ Trm during pregnancy. Tissue densities of Trm increased >5 fold prior to implantation (E3.5), and returned to baseline by E7.5 in all uterine tissue layers. Cognate peptide injection into the uterine lumen on E5.5 moreover induced a >2-fold increase in Trm tissue densities and Trm CD69 expression in all uterine tissues, as well as robust IFN␥ and TNF␣ production and degranulation. Peptide stimulation also induced the recruitment of B cells and antigen non-specific CD8 T cells to the virgin and E3.5 uterus, and to the E7.5 myometrium and inter-implantation sites. In contrast, Trm stimulation did not induce B or T cell recruitment to the decidua, nor did Trm activation cause fetal growth-restriction or demise even if the conceptus expressed ovalbumin as a surrogate fetal antigen. So, CD8+ Trm populate the gravid uterus and remain intrinsically functional in all uterine tissue layers, but are able to recruit immune cells only outside the decidua. These results are consistent with previously described mechanisms that limit T cell recruitment to the decidua, and reveal an additional way that the decidua attenuates immunological threats to the conceptus. http://dx.doi.org/10.1016/j.jri.2016.04.269 P2-51 RANKL promotes and maintains decidualization of human endometrial stromal cells triggered by PGE2 Wen-Jie Zhou, Ming-Qing Li, Da-Jin Li Laboratory for Reproductive Immunology, Institute of Obstetrics & Gynecology, Fudan University, Shanghai, China Decidualization is an essential preparation of human endometrium for implantation, although it has been shown that locally produced and temporally regulated products such as
http://dx.doi.org/10.1016/j.jri.2016.04.270 P2-52 Regulation of microRNA expression in CD4+T cells from the human endometrium and cervix by sex hormones Mickey V. Patel, Richard M. Rossoll, Charles R. Wira Geisel School of Medicine at Dartmouth, Hanover, NH, USA Previously we showed that endometrial (EM) CD4+T cells are resistant to HIV infection compared to those from the cervix (CX). However, the role of miRNAs in modulating EM and CX CD4+T cell susceptibility to HIV, and their regulation by estradiol (E2) is unknown. EM and CX CD4+T cells were isolated by negative magnetic bead selection from matched surgical tissues of pre- & post-menopausal women. CD4+T cells were treated for 24–72 h with E2 (5 × 10−8 M) & P (1 × 10−7 M). Total RNA was recovered and levels of anti-HIV miRNAs (miR20, 29, 31, 155 & Let7a) determined by RT-PCR. Expression of the anti-HIV miRNAs miR20 & Let7a was greater in EM than in CX CD4+T cells, with no differences in miR29 & 31. In contrast, the anti-HIV miR155 was present at higher levels in CX compared to EM CD4+T cells. Only miR21 was upregulated by E2 in EM CD4+T cells. When stratified by age (<45, 45–55, >55 yr), anti-HIV miR20, miR31 and Let7a expression in EM CD4+T cells were highest in women < 45 yr, while miR155 expression was highest in women 45–55 yr. Pro-HIV miR34 was highest in EM CD4+T cells from women > 55 yr. Higher expression of miR20 & Let7a in EM CD4+T cells may contribute to increased resistance to HIV infection. Regulation by E2 suggests that miRNA levels may change during the menstrual cycle altering susceptibility to HIV infection. Furthermore, changes in expression with age suggest that the contribution of miRNA to HIV susceptibility varies between pre- and postmenopausal women. http://dx.doi.org/10.1016/j.jri.2016.04.271
Abstracts / Journal of Reproductive Immunology 115 (2016) 71–90
as controls. On gestation day (gd) 15.5 and 18.5, fetal lung development was assessed histologically and the mRNA expression of regulatory proteins and differentiation markers was quantified by quantitative polymerase chain reaction. Stress challenge did not profoundly affect fetal lung development in male fetuses. However, female stress-challenged fetuses displayed less extensive terminal sac areas surrounded by thicker mesenchyme together with lower expression of insulin- like growth factor 1 receptor and surfactant protein-A than female control fetuses. Taken together, these findings suggest that prenatal stress induces a developmental delay of the lungs, evidenced by impaired branching, mesenchymal reduction and alveolarization in a sex-specific manner. This impaired lung development may increase the risk for airway diseases later in life, especially in the female offspring.
IL-11, prostaglandin E2 (PGE2) are involved in this process, the molecular mechanisms of it are not well understood. Here we found the expression of nuclear factor-kappaB receptor/nuclear factor-kappaB ligand (RANK/RANKL) in endometrial stromal cells (ESCs) was significantly lower than that in decidual stromal cells (DSCs). Compared to estrogen plus progesterone and cAMP, PGE2 obviously up-regulated the expression of member RANKL (mRANKL) and RANK on the surface of decidualized ESCs models in vitro, and this effect could inhibited by anti-human IL-1, IL-11 or IL-15 neutralizing antibody. In addition, mRANKL accelerated the process of decidualization in ESCs induced by PGE2 and up-regulated CD82 expression in DSCs, but not ESCs during decidualization. These results suggest that RANKL can stimulate decidualization of ESC derived by PGE2 and maintain the decidualization status of DSCs.
http://dx.doi.org/10.1016/j.jri.2016.04.268 P2-50 Presence and functionality of resident memory CD8 T cells in the pregnant mouse uterus Emiel D. Post Uiterweer, Johan Siewiera, Patrice Nancy, Adrian Erlebacher Department of Pathology, NYU School of Medicine, New York City, NY, USA Resident memory T cells (Trm), a newly described T cell subset, possess a robust ability to induce local inflammation and lymphocyte recruitment, thus raising questions about their potential impact on pregnancy success if present and active within the pregnant uterus. Here, we studied the behavior of ovalbuminspecific uterine CD8+ Trm during pregnancy. Tissue densities of Trm increased >5 fold prior to implantation (E3.5), and returned to baseline by E7.5 in all uterine tissue layers. Cognate peptide injection into the uterine lumen on E5.5 moreover induced a >2-fold increase in Trm tissue densities and Trm CD69 expression in all uterine tissues, as well as robust IFN␥ and TNF␣ production and degranulation. Peptide stimulation also induced the recruitment of B cells and antigen non-specific CD8 T cells to the virgin and E3.5 uterus, and to the E7.5 myometrium and inter-implantation sites. In contrast, Trm stimulation did not induce B or T cell recruitment to the decidua, nor did Trm activation cause fetal growth-restriction or demise even if the conceptus expressed ovalbumin as a surrogate fetal antigen. So, CD8+ Trm populate the gravid uterus and remain intrinsically functional in all uterine tissue layers, but are able to recruit immune cells only outside the decidua. These results are consistent with previously described mechanisms that limit T cell recruitment to the decidua, and reveal an additional way that the decidua attenuates immunological threats to the conceptus. http://dx.doi.org/10.1016/j.jri.2016.04.269 P2-51 RANKL promotes and maintains decidualization of human endometrial stromal cells triggered by PGE2 Wen-Jie Zhou, Ming-Qing Li, Da-Jin Li Laboratory for Reproductive Immunology, Institute of Obstetrics & Gynecology, Fudan University, Shanghai, China Decidualization is an essential preparation of human endometrium for implantation, although it has been shown that locally produced and temporally regulated products such as
http://dx.doi.org/10.1016/j.jri.2016.04.270 P2-52 Regulation of microRNA expression in CD4+T cells from the human endometrium and cervix by sex hormones Mickey V. Patel, Richard M. Rossoll, Charles R. Wira Geisel School of Medicine at Dartmouth, Hanover, NH, USA Previously we showed that endometrial (EM) CD4+T cells are resistant to HIV infection compared to those from the cervix (CX). However, the role of miRNAs in modulating EM and CX CD4+T cell susceptibility to HIV, and their regulation by estradiol (E2) is unknown. EM and CX CD4+T cells were isolated by negative magnetic bead selection from matched surgical tissues of pre- & post-menopausal women. CD4+T cells were treated for 24–72 h with E2 (5 × 10−8 M) & P (1 × 10−7 M). Total RNA was recovered and levels of anti-HIV miRNAs (miR20, 29, 31, 155 & Let7a) determined by RT-PCR. Expression of the anti-HIV miRNAs miR20 & Let7a was greater in EM than in CX CD4+T cells, with no differences in miR29 & 31. In contrast, the anti-HIV miR155 was present at higher levels in CX compared to EM CD4+T cells. Only miR21 was upregulated by E2 in EM CD4+T cells. When stratified by age (<45, 45–55, >55 yr), anti-HIV miR20, miR31 and Let7a expression in EM CD4+T cells were highest in women < 45 yr, while miR155 expression was highest in women 45–55 yr. Pro-HIV miR34 was highest in EM CD4+T cells from women > 55 yr. Higher expression of miR20 & Let7a in EM CD4+T cells may contribute to increased resistance to HIV infection. Regulation by E2 suggests that miRNA levels may change during the menstrual cycle altering susceptibility to HIV infection. Furthermore, changes in expression with age suggest that the contribution of miRNA to HIV susceptibility varies between pre- and postmenopausal women. http://dx.doi.org/10.1016/j.jri.2016.04.271