An endometrial immune atlas across the female menstrual cycle reveals lymphoid aggregates compromise pregnancy

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.

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Publication Details

Journal
Nature Communications
Published
2026-08-21
DOI
https://doi.org/10.1038/s41467-026-76937-y
Primary Topic
Reproductive System and Pregnancy
Type
article
Field-Weighted Citation Impact
0.00

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article

An endometrial immune atlas across the female menstrual cycle reveals lymphoid aggregates compromise pregnancy

Lijun Ding, Aiping Qin, Lianghui Diao, Xiaoshan Shi et al.
Nature Communications
Reproductive System and Pregnancy
article

An endometrial immune atlas across the female menstrual cycle reveals lymphoid aggregates compromise pregnancy

Lijun Ding, Aiping Qin, Lianghui Diao, Xiaoshan Shi, Yong Zeng, Yiyi Su, Shuyi Yu, Nengming Xiao, Elizabeth Soczewski, Udo R. Markert, Songchen Cai, Wanze Chen, Jana Pastuschek, Lingtao Yang, Dunja Baston-Buest, Kairui Mao, Tailang Yin, Astrid Schmidt, Hanjie Li, Wenjuan Liu, Hang Fu, Haixiang Sun, Shuang-Yin Wang, Huan Ma, Qiyuan Li, Chunyu Huang, Meilan Mo, Ruochun Lian, Linlin Wang, Jing Yang, Yuying Zhang, Fenghua Liu, Yuye Li, Xiaoyan Chen, Hao Wang, Alexandra P. Bielfeld, Zhenwei Lan, Fan Yang
article en

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.

Nature Communications
Guangxi Medical University (CN), Xiamen University (CN), Wuhan University (CN), First Affiliated Hospital of Xiamen University (CN), Düsseldorf University Hospital (DE), Shenzhen Maternity and Child Healthcare Hospital (CN), Nanjing Drum Tower Hospital (CN), The People's Hospital of Guangxi Zhuang Autonomous Region (CN), First Affiliated Hospital of GuangXi Medical University (CN), Jena University Hospital (DE), Renmin Hospital of Wuhan University (CN), Guangdong Province Women and Children Hospital (CN), Shenzhen Institutes of Advanced Technology (CN), Shenzhen Zhongshan Urological Hospital (CN), Jinling Institute of Technology (CN), Heinrich Heine University Düsseldorf (DE), Xiamen University of Technology (CN), Nanjing University (CN)
National Natural Science Foundation of China, Science, Technology and Innovation Commission of Shenzhen Municipality
Good health and well-being
Openalex Percentile: Top 16%
Reproductive System and Pregnancy
DOIOpen Access PDFOpenAlex
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