{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:59:57Z","timestamp":1793710797861,"version":"4.6.1"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Government | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["394570"],"award-info":[{"award-number":["394570"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endometriosis is a chronic inflammatory disease in which endometrial-like tissue grows ectopically, resulting in pelvic pain and infertility. IL-23 is a key contributor in the development and differentiation of TH17 cells, driving TH17 cells toward a pathogenic profile. In a variety of inflammatory and autoimmune disorders, TH17 cells secrete proinflammatory cytokines, including IL-17, contributing to disease pathophysiology. Our studies and others have implicated IL-17 and TH17 cell dysregulation in endometriosis, which is associated with disease severity. In this article, we address whether IL-23\u2013driven TH17 cells contribute to cardinal features of lesion proliferation, vascularization, and inflammation in endometriosis using patient samples, representative cell lines, and our established mouse model of endometriosis. The results indicated dysregulated expression of key genes in the IL-23\/TH17 axis in patient ectopic and eutopic endometrial samples and increased IL-23 protein in patient plasma compared with controls. In vitro studies using primary human TH cells determined that rIL-23 mixture treatment increased pathogenic TH17 cell frequency. Similarly, rIL-23 treatment of cell lines (12Z cells, EECCs, HUVECs, and hESCs) representative of the endometriotic lesion microenvironment increased cytokines and growth factors, which play a role in lesion establishment and maintenance. In a syngeneic mouse model of endometriosis, rIL-23 treatment altered numbers of myeloid and T cell subsets in peritoneal fluid and increased giant cells within the lesion. Lesions from rIL-23\u2013treated mice did not reveal significant alterations in proliferation\/vascularization, although trends of increased proliferation and vascularization were observed. Collectively, these findings provide insights into the impact of the IL-23\/TH17 axis on local immune dysfunction and broadly on endometriosis pathophysiology.<\/jats:p>","DOI":"10.4049\/jimmunol.2400018","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T09:32:22Z","timestamp":1710149542000},"page":"1428-1441","source":"Crossref","is-referenced-by-count":29,"title":["The Dysregulated IL-23\/TH17 Axis in Endometriosis Pathophysiology"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8061-0631","authenticated-orcid":false,"given":"Danielle J","family":"Sisnett","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-1024","authenticated-orcid":false,"given":"Katherine B","family":"Zutautas","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshavardhan","family":"Lingegowda","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9541-5281","authenticated-orcid":false,"given":"Soo Hyun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-9221","authenticated-orcid":false,"given":"Alison","family":"McCallion","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Bougie","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]},{"name":"Department of Obstetrics and Gynaecology, Kingston Health Sciences Centre , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A","family":"Lessey","sequence":"additional","affiliation":[{"name":"School of Medicine, Wake Forest University , Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-050X","authenticated-orcid":false,"given":"Chandrakant","family":"Tayade","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University , Kingston, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"2025020405484097900_r1","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1056\/NEJMcp1000274","article-title":"Endometriosis","volume":"362","author":"Giudice","year":"2010","journal-title":"N. 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