An endometrial immune atlas across the female menstrual cycle reveals lymphoid aggregates compromise pregnancy
Year: 2026
Type: article
Study design: Observational Study
Abstract: The human endometrial immune landscape is critical for homeostasis and pregnancy success, yet its dynamic remodeling across the menstrual cycle and in pathology remains poorly characterized. Here, we construct a comprehensive immune cell atlas of the human endometrium, profiling 53 healthy women and 34 chronic endometritis (CE) patients across precisely staged menstrual cycle phases. Our analysis reveals NK and T cells as dominant constituents, with NK cells increasing while T cells decreasing progressively from proliferative to secretory phase. B cells, mast cells, and innate lymphoid cells remain consistently low. Of the two tissue-resident NK subsets, CD11c⁺ NK cells accumulate during the secretory phase and early pregnancy. CE disrupts this landscape, marked by CD11c⁺ NK cell reduction, local B cell proliferation and differentiation, and formation of ectopic lymphoid aggregates comprising germinal-center-B-like cells and T follicular helper-like cells. Using a murine CE model and a subsequent multi-center cohort study we demonstrate that these aggregates compromise pregnancy outcomes in a Tfh-like-cell-dependent manner. Collectively, we establish a detailed immune cell atlas of the cycling human endometrium and define a pathogenic mechanism for adverse pregnancy outcomes. The immune landscape of human endometrium is remodeled across the menstrual cycle. The authors here provide a comprehensive immune atlas of these changes, and show that ectopic lymphoid aggregates, composed of germinal-center-B-like cells and T follicular helper-like cells, form in mouse and human chronic endometritis, which might lead to adverse pregnancy outcomes.
Source: Nature Communications
Authors: Lingtao Yang, Jing Yang, Yuye Li, Yiyi Su, Huan Ma, Songchen Cai, Meilan Mo, Lijun Ding, Chunyu Huang, Fenghua Liu, Aiping Qin, Alexandra P. Bielfeld, Udo R. Markert, Shuyi Yu, Linlin Wang, Ruochun Lian, Fu Hang, Wenjuan Liu, Elizabeth Soczewski, Astrid Schmidt, Jana Pastuschek, Dunja M. Baston-Buest, Nengming Xiao, Kairui Mao, Hao Wang, Xiaoyan Chen, Zhenwei Lan, Yuying Zhang, Tailang Yin, Wanze Chen, Xiaoshan Shi, Shuangyin Wang, Fan Yang, Haixiang Sun, Yong Zeng, Qiyuan Li, Lianghui Diao, Hanjie Li
Institutions: Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Shenzhen Zhongshan Urological Hospital, Shenzhen Institute of Synthetic Biology, Xiamen University, First Affiliated Hospital of Xiamen University, Chinese University of Hong Kong, Chinese University of Hong Kong, Shenzhen, Nanjing Drum Tower Hospital, Nanjing University, Guangdong Province Women and Children Hospital, First Affiliated Hospital of GuangXi Medical University, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, Jena University Hospital, Wuhan University, Renmin Hospital of Wuhan University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7203875918
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