Epithelial Cells in Endometriosis and Adenomyosis Upregulate STING Expression

In response to cytosolic DNA, stimulator of interferon gene (STING) initiates and orchestrates host’s innate immunity by inducing type I interferon. Since endometriosis is a chronic inflammatory disorder, we sought to determine whether STING pathway is activated in ectopic endometrium in comparison to eutopic endometrium. Immunohistochemistry was employed in evaluating the expression levels of STING in normal endometrium, endometriosis, and adenomyosis. The density of CD45+ intraepithelial lymphocytes was correlated with STING expression levels. A total of 39 cases of endometriosis and/or adenomyosis with normal endometrium were analyzed. Among them, 32 had adenomyosis, 26 had endometriosis, and 19 have both lesions. STING protein expression is mainly evident in the cytoplasm of epithelial cells but much less in stromal cells. Based on H-score, we found that the STING expression levels were significantly higher in the epithelial cells of adenomyosis and endometriosis than in eutopic endometrium (132.7 ± 12.20, 119.6 ± 12.57 vs. 19.74 ± 5.96, p < 0.0001). There was no significant difference in STING expression level between endometriosis and adenomyosis. More intraepithelial lymphocytes were detected in endometriosis and adenomyosis lesions than endometrium (5.60 ± 0.70%, 4.95 ± 0.54% vs. 1.25 ± 0.12%, p < 0.0001). A positive correlation between STING expression and intraepithelial lymphocytic infiltrate was observed (p < 0.0001). In summary, STING was upregulated in the epithelium of ectopic endometrium as compared to eutopic endometrium. Its expression levels correlate with the degree of intraepithelial lymphocyte infiltration, suggesting a role in promoting chronic inflammation of ectopic endometrium. Similar content being viewed by others

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Mayassi T, Jabri B. Human intraepithelial lymphocytes. Mucosal Immunol. 2018;11:1281–9. Acknowledgments This study was supported by Richard W. TeLinde endowment for gynecologic pathology research from the Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine and Endometriosis Foundation of America. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of Interest The authors declare no competing or financial interests. Electronic supplementary material ESM 1 (download JPG ) (JPG 1304 kb) Rights and permissions About this article Cite this article Qu, H., Li, L., Wang, TL. et al. Epithelial Cells in Endometriosis and Adenomyosis Upregulate STING Expression. Reprod. Sci. 27, 1276–1284 (2020). https://doi.org/10.1007/s43032-019-00127-z Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-019-00127-z