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galectin-9/cd44 signaling-induced activation on cd11c high macrophages contribute to the compromised spiral artery remodeling in preeclampsia

Galectin-9/CD44 signaling-induced activation on CD11c high m...

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第十四届全国免疫学学术大会

作者： Yanhong Li Yifei Sang Ling Xu Jiaijia Chen Dajin Li Meirong Du Laboratory for Reproductive Immunology Hospital of Obstetrics and GynecologyFudan University Shanghai Medical College

Macrophages(Mφ) are involved in spiral artery remodeling(SAR) in normal ***,the underlying mechanism of Mcp involved in preeclampsia(PE) remains ***,we found that trophoblasts-derived galectin-9(gal-9) was highly expressed in placenta and plasma of PE patients as well as in the PE mouse ***-9 administered caused development of PE features,whereas gal-9 blockade was *** found that rhGal-9 treatment enhanced the adhesion of decidual Mcp to extravillous trophoblast(EVT) cells via activating FAK/Src ***,gal-9 induced the expansion of cd11 c Mcp and enhanced their activated phenotype via interacting with ***-1(3 and TNF-α produced by cd11 c Mcp after gal-9 stimulation remarkably increased the apoptosis of EVT cells,which is adverse to *** addition,gal-9/cd44 interaction promoted the ubiquitination of RIPK1 and induced autophagy via the AMPK-mTOR *** degradation of ubiquitinated PKR1 mediated by the autophagy manner,led to the decreased angiogenic factor IL-8 production by ***,the tube formation and SAR were impaired due to the less ***,our results revealed a new mechanism by which Mφ mediated abnormal SAR,and gal-9/cd44 is suggested to be a potential therapeutic target for PE.

关键词： galectin-9/cd44 cd11chigh macrophage spiral artery remodeling autophagy ubiquitination preeclampsia

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galectin-9/cd44 signaling-induced pro-inflammatory cd11chigh macrophages contribute to the excessive apoptosis of trophoblast cells in preeclampsia

Galectin-9/CD44 signaling-induced pro-inflammatory CD11chigh...

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第十一届全国免疫学学术大会

作者： Li Yanhong Lin yikong Tian ye Zhang di Ye yunzhen Li dajin Du meirong Laboratory for Reproductive Immunology Hospital and Institute of Obstetrics and GynecologyFudan University Shanghai Medical CollegeShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Beijing Normal University

Macrophages abundant in decidua are associated with spiral artery remodeling in normal pregnancy. In preeclampsia, increased numbers and abnormal activation of macrophages are found at the maternal-fetal interface. However, the underlying mechanism of macrophages involved in preeclampsia remains unknown. In this study, we found that trophoblastsderived galectin-9(gal-9) was significantly higher in both placenta and plasma of the preeclampsia patients compared with the healthy control group. Rh Gal-9 treatment induced the expansion of cd11 chigh macrophages exhibited a more activated phenotype with notably higher expression of co-stimulatory molecules cd80, cd86 and cd16. In addition, inflammatory cytokines IL-1β and TNF-α produced by cd11 chigh macrophages were remarkably increased after gal-9 stimulation. Trophoblast cells cultured with the supernatant of gal-9-treated macrophages showed significantly promoted apoptosis, which is adverse to the process of spiral artery remodeling. This effect on trophoblast cells by macrophages was due to the cooperation of gal-9-triggered IL-1β and TNF-α and could be abrogated by blocking the gal-9 signaling using anti-cd44 neutralizing antibody. No difference was obtained in the culture system with anti-Tim-3 neutralizing antibody or not. Further investigation showed that the mRNA and protein expression of cd44 on cd11 chigh macrophages were particularly higher than that on cd11 clow macrophages, confirming that the macrophages-mediated modulation on trophoblast cells was via gal-9 binding to cd44 and their interactions. Therefore, our results suggest that higher expression of galectin-9 by trophoblast cells in preeclampsia induces the expansion of cd11 chigh macrophages and enhances their pro-inflammatory propensity in a cd44-dependent manner, which in turn contributes to the excessive apoptosis of trophoblast cells.

关键词： galectin-9/cd44 cd11chigh macrophage trophoblasts preeclampsia

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Increased galectin-9 in pre-eclampsia impedes spiral artery remolding

Increased galectin-9 in pre-eclampsia impedes spiral artery ...

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第十二届全国免疫学学术大会

作者：李彦虹林懿空田野叶云贞李大金杜美蓉复旦大学附属妇产科医院北京师范大学

Macrophages(Mm) are involved in spiral artery remodeling(SAR) in normal ***,the underlying mechanism of Mm involved in preeclampsia(PE) remains ***,we found that trophoblasts-derived galectin-9(gal-9)was significantly higher in both placenta and plasma of PE patients than that of the healthy ***-9 treatment enhanced the adhesion of decidual Mcp to EVT cells via activating FAK/Src ***,gal-9 binding with cd44,induced the expansion of cd 11 c

关键词： galectin-9/cd44 cd11chigh macrophage spiral artery remodeling autophagy preeclampsia

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