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.