Work

Estrogen-triggered neutrophil extracellular traps fuel sterile inflammation via NKCC1

Year: 2026

Type: preprint

Abstract: Disorders of the menstrual cycle or exposure to external pathogens lead to uterus-related diseases, such as endometrial hyperplasia (EH) and endometritis (EN). We constructed a multiomics method to compare the molecular differences between estrogen-induced hyperplastic endometrium and infection-triggered inflammatory endometrium at the single-cell level. A unique neutrophil subpopulation that expresses Estrogen Receptor 1 (ESR1) was newly identified to be involved in EH development. Distinct from the infectious state, estrogen-induced NETs were mainly a consequence of ERα binding to HMGN2. Mechanistically, NETs could bind to NKCC1 and promote imbalance of ion homeostasis in endometrial epithelial cells, leading to cell proliferation and EH. Pharmacologically, aspirin was found to inhibit NET formation and alleviated EH in a nonhuman primate model by directly acetylating at K64 and K82 of HMGN2. Collectively, this study highlights neutrophil heterogeneity in sterile inflammation or infectious inflammation, providing a novel nonhormonal treatment strategy for the patients with estrogen abnormalities.

Source: Research Square

DOI: 10.21203/rs.3.rs-11368963/v1

Authors: Yang Sun, Jiao Qu, Wen Fang, Tao Zhang, Wei Liu, Yan Ding, Songjun Liu, Xinran Cao, Ning Wan, Hui Ye, Xianjia Qi, Tian Xu, Yan Li, Dijun Chen, Wen Lv, Qiang Xu

Institutions: Nanjing University, Model Animal Research Center, State Key Laboratory of Pharmaceutical Biotechnology, Zhejiang Chinese Medical University, Tongde Hospital of Zhejiang Province, China Pharmaceutical University, Nanjing University of Chinese Medicine

Language: English

Topic: Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7225423242

Cites:

Cited by:

Related to: 10