TY - JOUR
T1 - Epithelial Cells in Endometriosis and Adenomyosis Upregulate STING Expression
AU - Qu, Hong
AU - Li, Lihong
AU - Wang, Tian Li
AU - Seckin, Tamer
AU - Segars, James
AU - Shih, Ie Ming
N1 - Funding Information:
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.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Adenomyosis
KW - Endometriosis
KW - Inflammation
KW - STING
UR - http://www.scopus.com/inward/record.url?scp=85080854538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85080854538&partnerID=8YFLogxK
U2 - 10.1007/s43032-019-00127-z
DO - 10.1007/s43032-019-00127-z
M3 - Article
C2 - 32046461
AN - SCOPUS:85080854538
VL - 27
SP - 1276
EP - 1284
JO - Reproductive Sciences
JF - Reproductive Sciences
SN - 1933-7191
IS - 6
ER -