Page 13 - HKSEMR2020 Programme book

Oral Presentation (Basic Science) Abstracts

The role of placenta-derived exosomes in the acquisition of an M2

phenotype in human decidual macrophages

Kun-Feng Bai, Cheuk-Lun Lee, Philip C.N. Chiu
Department of Obstetrics and Gynecology, The University of Hong Kong, Pokfulam Road, Hong Kong SAR;
Shenzhen Key Laboratory of Fertility Regulation, Department of Obstetrics and Gynecology, The University of Hong
Kong-Shenzhen Hospital

Introduction / Background / Objectives: conditioned medium by our established protocols using ultra-
filtration and ultra-centrifugation. Human monocytes were isolated
Exosomes are nano-sized vesicles (diameter < 100 nm) released
by cells that play a crucial role in cell-cell communication. from female blood by immunomagnetic isolation and were
During pregnancy, the level of placenta-derived exosomes differentiated into macrophages by macrophage colony-stimulating
(pEXO) in maternal blood continuously increase along with factor (M-CSF; 50 ng/mL). Human monocyte-derived macrophages
gestational progression. Their concentration will increase further were further treated with pEXO (20 μg/mL) for another 24 hours.
in pregnancies complicated by gestational diabetes mellitus and The phenotypes, viability, phagocytic activity and cytokine
preeclampsia. secretion profile of the pEXO-treated macrophages were analyzed.
Trophoblast migration and invasion were investigated by using
Maternal immune tolerance toward to the semi-allograft fetus pEXO-treated macrophage-conditioned medium.
is key to a successful pregnancy. Decidual macrophages
comprise the 2nd largest group of innate immune cells in the
decidualized endometrium. Decidual macrophages display the Results / Outcomes:
transcriptional profile of both classically activated macrophages Placenta-derived exosomes treatment significantly induced
(M1 macrophages), which secrete cytokines such as interleukin the expression levels of alternatively activated macrophages
(IL)-6 and tumour necrosis factor (TNF)α which are associated with (M2) markers, including CD163, CD206, IDO-1 and IL-10 in the
immune activation, and alternatively activated macrophages (M2 differentiated macrophages. Interestingly, HDAC9 was the only
macrophages), which secrete high levels of anti-inflammatory histone deacetylase upon down-regulated pEXO treatment.
cytokines IL-10 and TGF-β. Decidual macrophage polarization Knockdown with HDAC9 small interfering RNA and HDAC inhibitor
involves a complex local microenvironment including the stimuli treatment also promoted macrophage polarization. Specifically,
from maternal decidua-derived factors as well as the fetal the up-regulation of Wnt5a was associated with down-regulated
placenta-derived factors. Despite the importance of decidual HDAC9 expression in pEXO-macrophages. Moreover, the
macrophages in pregnancy, little is known about the factors conditioned medium of pEXO-treated macrophages promoted
regulating their polarization and functions.
trophoblast migration and invasion, which was mediated by Wnt5a.
Decidual macrophages support the development of the fetus by Tube formation and endothelial cell migration were reduced upon
mediating the spiral artery remodelling functions of the extravillous conditioned medium treatment. Exosome treatment also down-
trophoblast. Signalling pathways such as the wingless-related regulated the secretion of TNFα and MIP-1α by the differentiated
integration site (Wnt) are involved in placentation and uterine macrophages. Thus, the pEXO-modified epigenetic signature is
spiral artery remodelling. For example, decidual macrophage- essential for reprogramming decidual macrophages and supporting
derived Wnt5a has been demonstrated to promote trophoblast maternal tolerance.
proliferation and invasion. More interestingly, Wnt5a has been
inversely correlated with HDAC9 activity in cancer. However,
whether epigenetic modifications such as histone acetylation and Conclusion:
deacetylation lead to macrophage polarization and activation of Placental exosomes drive the acquisition of M2 phenotype
Wnt signaling is unknown. in human decidual macrophages, which promotes placental

development by mediating trophoblast functions.
Methods:
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pEXO were isolated from human first-trimester placenta explant-