Results
| PMID | 28300844 |
| Gene Name | IL10 |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Associated genes | IL10, IL27, IL6 and TGFB1 |
| Other associated phenotypes |
Endometriosis |
|
Cell Death Dis. 2017 Mar 16;8(3):e2666. doi: 10.1038/cddis.2017.95. Chang, Kai-Kai| Liu, Li-Bing| Jin, Li-Ping| Zhang, Bing| Mei, Jie| Li, Hui| Wei, Chun-Yan| Zhou, Wen-Jie| Zhu, Xiao-Yong| Shao, Jun| Li, Da-Jin| Li, Ming-Qing Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, People's Republic of China.| Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, People's R Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10(+)Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-beta. Compared with peripheral CD4(+) T cells, endometrial CD4(+) T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-beta) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORgammat), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10(+)Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10(+)Th17 cells. Mesh Terms: Adult| CD4-Positive T-Lymphocytes/metabolism/pathology| Cell Differentiation/physiology| Disease Progression| Endometriosis/*metabolism/pathology| Endometrium/metabolism/pathology| Female| Humans| Interleukin-10/*metabolism| Interleukin-6/metabol |
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