CD11d+ NK cell-derived exosomal HSPB1 suppresses angiogenesis in adenomyosis

Our study aimed to explore the mechanisms underlying abnormal angiogenesis in adenomyosis (AM). Endometria of internal adenomyosis (AM-in) and external adenomyosis (AM-ex) were collected for single-cell RNA-sequencing. Cells showing consistent change tendency in AM-in and AM-ex groups were selected as the research target. Functional experiments were performed to assess angiogenesis regulation. Specific proteins in target cell-derived exosomes and the signaling pathways involved were analyzed. In the single-cell landscape of the endometrium in adenomyosis, fibroblasts and T cells had the largest number in non-immune and immune cells. CD11d+ NK cell was found to be negatively correlated with angiogenesis. CD11d+ NK cell-derived exosomes inhibited tube formation and cell proliferation and migration; interrupting exosome secretion could attenuate the inhibitory effects. A total of 175 unique proteins were identified in CD11d+ NK cell-derived exosomes, primarily involved in angiogenesis-related signaling pathways. One protein, HSPB1, was annotated in the star MAPK signaling pathway. Interference of HSPB1 could regulate angiogenesis inhibited by CD11d+ NK cell-derived exosomes. In summary, cell compositions and functions in the endometrium of adenomyosis were heterogeneous. CD11d+ NK cells suppress angiogenesis through exosomal protein HSPB1, offering a cellular-level understanding of the angiogenesis regulation in adenomyosis from the perspective of immune cells. This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 6 digital issues and online access to articles 111,21 € per year only 18,54 € per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Data availability Sequence data that support the findings of this study have been deposited in the NCBI (PRJNA1194743).

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This work was supported by the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-C-065) and by the Beijing Association of Holistic Integrative Medicine Project (No. ZHKY-2025-1869 (C006)). Author information Authors and Affiliations Contributions Ting Gui: performed experiments, analyzed data, interpreted results of experiments, prepared figures, drafted manuscript, and approved final version of manuscript. Duoduo Zhang: analyzed data, interpreted results of experiments, prepared figures, drafted manuscript. Qi Yu: conceived and designed the research, edited and revised the manuscript, and approved the final version of the manuscript. Shan Deng: conceived and designed the research, edited and revised the manuscript, and approved the final version of the manuscript. Corresponding authors Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Gui, T., Zhang, D., Yu, Q. et al. CD11d+ NK cell-derived exosomal HSPB1 suppresses angiogenesis in adenomyosis. Genes Immun 27, 245–257 (2026). https://doi.org/10.1038/s41435-026-00379-1 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1038/s41435-026-00379-1