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IL‐10 from plasmacytoid dendritic cells promotes angiogenesis in the early stage of endometriosis
Journal of Pathology ( IF 5.942 ) 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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