T helper 17 axis and endometrial macrophage disruption in menstrual effluent provides potential insights into the pathogenesis of endometriosis

Jessica E Miller; Harshavardhan Lingegowda; Danielle J Sisnett; Christine N Metz; Peter K Gregersen; Madhuri Koti; Chandrakant Tayade

doi:10.1016/j.xfss.2022.04.007

T helper 17 axis and endometrial macrophage disruption in menstrual effluent provides potential insights into the pathogenesis of endometriosis

F S Sci. 2022 Aug;3(3):279-287. doi: 10.1016/j.xfss.2022.04.007. Epub 2022 May 4.

Authors

Jessica E Miller¹, Harshavardhan Lingegowda¹, Danielle J Sisnett¹, Christine N Metz², Peter K Gregersen², Madhuri Koti³, Chandrakant Tayade⁴

Affiliations

¹ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
² The Feinstein Institutes for Medical Research, Institute of Molecular Medicine, Northwell Health, Manhasset, New York.
³ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Department of Obstetrics and Gynecology, Kingston General Hospital, Kingston, Ontario, Canada.
⁴ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. Electronic address: tayadec@queensu.ca.

PMID: 35697654
DOI: 10.1016/j.xfss.2022.04.007

Abstract

Objective: To identify immune cells, cytokines, and immune cell transcriptome in the menstrual effluent (ME) of women with endometriosis compared with that of healthy donors.

Design: Live immune cells were isolated from human ME samples and were analyzed by flow cytometry to identify various immune cell populations. Selected cytokines from the same patients were evaluated using multiplex cytokine analyses. The transcriptome of the immune cell population was subsequently profiled using NanoString nCounter's PanCancer Immune panel.

Setting: Academic institution.

Patient(s): Surgically confirmed endometriosis patients (n = 14) and healthy fertile donors (n = 19).

Intervention(s): None.

Main outcome measure(s): In-depth immune cell profiling of ME obtained from women with endometriosis compared with that of healthy donors.

Result(s): ME analysis revealed that the number of T helper 17 (T_H17) cells was significantly lower in patients with endometriosis compared with that of healthy donors; the number of macrophages was also lower (P=.06) in the former. Multiplex cytokine analysis revealed significantly lower transforming growth factor α in the ME "serum" of patients with endometriosis. Transcriptomic analysis of CD45⁺ cells revealed 47 differentially expressed genes, mainly associated with the T_H17 axis (IL10, IL23A, and IL6), as well as genes associated with macrophage signaling/activation (CD74, CD83, CXCL16, and CCL3).

Conclusion(s): We demonstrate for the first time that the levels of T_H17 axis, macrophages, and transforming growth factor α were altered in the ME of women with endometriosis compared with that of healthy donors. These findings shed light on the potential immune pathways that could partly explain the pathogenesis and progression of endometriosis. Future large-scale studies on ME samples are warranted to exploit the use of these markers to study the pathogenesis of endometriosis.

Keywords: T helper 17 cells; endometriosis; immune; macrophage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines / immunology
Endometriosis* / pathology
Endometrium
Female
Humans
Macrophages* / immunology
Th17 Cells* / immunology
Transforming Growth Factor alpha / immunology

Substances

Cytokines
Transforming Growth Factor alpha