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IL-10 from plasmacytoid dendritic cells promotes angiogenesis in the early stage of endometriosis.
The Journal of Pathology ( IF 5.979 ) Pub Date : 2019-10-06 , DOI: 10.1002/path.5339
Jau-Ling Suen,Yu Chang,Yu-Shiang Shiu,Chia-Yi Hsu,Pooja Sharma,Chien-Chih Chiu,Yi-Ju Chen,Tzyh-Chyuan Hour,Eing-Mei Tsai

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. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
更新日期:2019-10-10

 

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