IL‐10 from plasmacytoid dendritic cells promotes angiogenesis in the early stage of endometriosis

Jau‐Ling Suen, Yu Chang, Yu‐Shiang Shiu, Yu-Shiang Shiu, Chia-Yi Hsu, Chia‐Yi Hsu, Pooja Sharma, Chien‐Chih Chiu, Chien-Chih Chiu, Yi-Ju Chen, Yi‐Ju Chen, Tzyh-Chyuan Hour, Tzyh‐Chyuan Hour, Eing-Mei Tsai, Eing‐Mei Tsai
The Journal of Pathology · 2019 · vol. 249(4) , pp. 485–497 · doi:10.1002/path.5339 · PMID:31418859 · W2967375519
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Plasmacytoid dendritic cell-derived IL-10 promotes early endometriosis development by stimulating VEGF-dependent pathological angiogenesis.

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Abstract

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. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Condition tags

mesh:D004715endometriosisendometrioma

MeSH descriptors

Dendritic Cells Endometriosis Endometrium Interleukin-10 Neovascularization, Pathologic Paracrine Communication Adoptive Transfer Adult Animals Apoptosis Cells, Cultured Coculture Techniques Dendritic Cells Dendritic Cells Dendritic Cells Disease Models, Animal Endometriosis Endometriosis Endometrium Female

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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Cited by (36)

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