PUBLICATION
IL-10 from plasmacytoid dendritic cells promotes angiogenesis in the early stage of endometriosis
- Authors
- Suen, J.L., Chang, Y., Shiu, Y.S., Hsu, C.Y., Sharma, P., Chiu, C.C., Chen, Y.J., Hour, T.C., Tsai, E.M.
- ID
- ZDB-PUB-190817-11
- Date
- 2019
- Source
- The Journal of pathology 249(4): 485-497 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Endometriosis, IL-10, Plasmacytoid dendritic cell, Zebrafish
- MeSH Terms
-
- Adoptive Transfer
- Adult
- Animals
- Apoptosis
- Cells, Cultured
- Coculture Techniques
- Dendritic Cells/metabolism*
- Dendritic Cells/pathology
- Dendritic Cells/transplantation
- Disease Models, Animal
- Endometriosis/metabolism*
- Endometriosis/pathology
- Endometrium/blood supply*
- Female
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Interleukin-10/deficiency
- Interleukin-10/genetics
- Interleukin-10/metabolism*
- Interleukin-3 Receptor alpha Subunit/metabolism
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Nude
- Middle Aged
- Neovascularization, Pathologic*
- Paracrine Communication*
- Receptors, Interleukin-10/metabolism
- Signal Transduction
- Young Adult
- Zebrafish
- PubMed
- 31418859 Full text @ J. Pathol.
Citation
Suen, J.L., Chang, Y., Shiu, Y.S., Hsu, C.Y., Sharma, P., Chiu, C.C., Chen, Y.J., Hour, T.C., Tsai, E.M. (2019) IL-10 from plasmacytoid dendritic cells promotes angiogenesis in the early stage of endometriosis. The Journal of pathology. 249(4):485-497.
Abstract
An elevated level of IL-10 has been considered a critical factor for the development of endometriosis; however, its detailed mechanism and causal relationship remain unclear. This study explored the cellular source and angiogenic activity of local IL-10 during the early stage of endometriosis. Using a surgical murine model, we found that localised treatment with exogenous recombinant IL-10 on the day of surgery significantly enhanced endometriotic lesion growth and angiogenesis, whereas blocking local IL-10 activity using mAbs significantly suppressed those effects. Adoptive transfer of Il10+/+ plasmacytoid dendritic cells into mice significantly enhanced lesion development, whereas Il10-/- plasmacytoid dendritic cells significantly inhibited lesion development. Furthermore, in vitro angiogenesis analyses demonstrated that the IL-10 and IL-10 receptor pathway stimulated the migratory and tube formation ability of HUVECs as well as ectopic endometrial mesenchymal stem cells through, at least in part, a VEGF-dependent pathway. We also found that recombinant IL-10 directly stimulated angiogenesis based on a Matrigel plug assay as well as a zebrafish model. Pathological results from human endometrioma tissues showed the increased infiltration of CD123+ plasmacytoid dendritic cells and higher percentages of cells that express the IL-10 receptor and CD31 as compared with the corresponding normal counterparts. Taken together, these results show that IL-10 secreted from local plasmacytoid dendritic cells promotes endometriosis development through pathological angiogenesis during the early disease stage. This study provides a scientific basis for a potential therapeutic strategy targeting the IL-10-IL-10 receptor pathway in the endometriotic milieu. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping