The Dysregulated IL-23/TH17 Axis in Endometriosis Pathophysiology
Danielle J Sisnett1, Katherine B Zutautas1, Jessica E Miller1
1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|March 11, 2024
Summary
Interleukin-23 (IL-23) drives T helper 17 (TH17) cells, contributing to endometriosis inflammation. Targeting this IL-23/TH17 pathway may offer new therapeutic strategies for endometriosis patients.
Area of Science:
- Immunology
- Reproductive Medicine
- Cell Biology
Background:
- Endometriosis is a chronic inflammatory condition linked to pelvic pain and infertility.
- T helper 17 (TH17) cells and their cytokine IL-17 are implicated in endometriosis pathophysiology.
- IL-23 is crucial for TH17 cell development and pathogenicity.
Purpose of the Study:
- To investigate the role of IL-23-driven TH17 cells in endometriosis lesion proliferation, vascularization, and inflammation.
- To analyze the IL-23/TH17 axis in patient samples and a mouse model of endometriosis.
Main Methods:
- Analysis of gene and protein expression in patient endometrial samples and plasma.
- In vitro studies using primary human T cells and endometriosis-associated cell lines treated with recombinant IL-23 (rIL-23).
- In vivo studies using a syngeneic mouse model of endometriosis with rIL-23 administration.
Main Results:
- Dysregulated IL-23/TH17 axis gene expression and elevated IL-23 protein in endometriosis patients.
- rIL-23 treatment increased pathogenic TH17 cell frequency in vitro.
- rIL-23 modulated immune cell populations and increased giant cells in mouse lesions, with trends toward increased proliferation and vascularization.
Conclusions:
- The IL-23/TH17 axis is dysregulated in endometriosis, influencing local immune dysfunction.
- IL-23 promotes features relevant to endometriosis pathophysiology, suggesting it as a therapeutic target.
- Further research into the IL-23/TH17 axis could reveal novel treatment strategies for endometriosis.
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