Reduction of myeloid derived suppressor cells by inhibiting Notch pathway prevents the progression of endometriosis in mice model

Jiang H, Huanhuan Jiang, Bi K, Kaihuan Bi, Wang K, Kangxia Wang, Zhimin Lu, Lu Z, Xu Y, Yuping Xu, Guo P, Peipei Guo, Caihua Li, Li C, Zhaolian Wei, Wei Z, Chen Y, Ya Chen, Yunxia Cao, Cao Y
International Immunopharmacology · 2020 · vol. 82 , pp. 106352 · doi:10.1016/j.intimp.2020.106352 · PMID:32143006 · W3009488614
article OA: closed CC0 ⤵ 10 in-corpus citations
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In a mouse model, inhibiting the Notch pathway reduced myeloid-derived suppressor cells and prevented endometriosis progression.

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Abstract

Growing evidence suggested that immune dysregulation is one of the crucial drivers to the development of endometriosis (EMS). Myeloid derived suppressor cells (MDSCs) represent a heterogeneous subset of immature myeloid cells, and have been reported to promote the onset and progression of EMS. Notch signaling pathway played a major role in immunological reactions. Studies have found Notch signaling pathway could regulate MDSCs. However, how the biological effects of Notch signaling pathway on MDSCs may work in EMS is still unknown. In our study, we first built an endometriosis induced mice model. Then we treated mice with DAPT, a Notch signaling pathway inhibitor, or saline. We found that the DAPT could prevent the progression of EMS. The ADAM17, Notch1, Jagged1 and Hes1 were overexpressed in EMS mice, however, when mice were treated with DAPT, the overexpression was reduced. Meanwhile, we found a lower level of MDSCs in the DAPT treated EMS mice as compared to EMS mice without DAPT, accompanied by an increase of T helper (TH) 17 cells and a decrease of regulatory T cells (Tregs). We also investigated the reactive oxygen species (ROS) in peritoneal and endometriotic cells. Our results showed that ROS level decreased in both peritoneal and endometriotic cells in the study group treated with DAPT. Overall, our study indicates for the first time that blockage of Notch signaling could lessen MDSCs and ROS, and therefore preventing the development of endometriosis.

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endometriosis

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