Popular Science Format in Academic and Research Column

Popular Science Format in Academic and Research Column

[Introduction]

Endometriosis is a chronic inflammation-associated and common benign gynecological disorder. It affects 6–10% of women of reproductive age with syndromes, including dysmenorrhea, dyspareunia, and infertility. Because endometriosis recurrence following conservative surgery is relatively high, it substantially affects patients’ daily activities.   

[Lost way of endometrial tissue]

What is the pathogenesis of endometriosis? The wildly accepted hypothesis nowadays is the “retrograde menstruation/transplantation theory. The endometrial tissue shed during the menstrual cycle flow from the uterus into the peritoneal cavity. The retrograded cells or tissue are cleared by white blood cells. During this process, it would locally happen mild and transient inflammation in peritoneal cavity. If the process between clearance and inflammation keeps balance, the ectopic endometrial tissue can be effectively cleared and the inflammation would not damage the tissue in peritoneal cavity. Therefore, the lost-way endometrial tissue would not become endometriotic tumor and disturb daily activity in women of reproductive age.     

[Dysregulated inflammation]

What might disturb the balance between clearance and inflammation when retrograde tissue loses its way into peritoneal cavity? The research team led by Dr. Jau-Ling Suen at Kaohsiung Medical University discovered that the high local activity of anti-inflammatory cytokine IL-10 may promote the growth of the endometriotic tissue. It has been demonstrated that IL-10 can control unwanted inflammation to avoid tissue damage; however, high activity or level of IL-10 may inhibit the functions of white blood cells and diminish the clearance of ectopic tissue. In addition, Dr. Suen and her colleges discovered that IL-10 can promote angiogenesis through IL-10R signaling in vitro and in vivo, including a murine model as well as a zebra fish model. Thus, the IL-10-mediated angiogenesis may promote the growth of endometriotic lesions through enhancing angiogenesis during the early stage of endometriosis. 

[The dual activity of IL-10]

These findings discovered by Dr. Suen’s team suggest that the dual functions of IL-10 with respect to suppressing immunity against unwanted cells and promoting angiogenesis in the microenvironment may substantially contribute to the development of endometriosis. The next question is which immune cell type can secrete IL-10 in the microenvironment, particularly during the early stage of disease? Using a surgery-induced endometriosis murine model, Dr. Suen’s team demonstrated that local plasmacytoid dendritic cell (pDC), a key innate cell type in viral immunity, can secrete IL-10 to enhance angiogenesis in and promote growth of endometriotic lesions. In addition, IL-10–secreting pDCs have been found in the human endometrioma tissues, in which higher percentages of cells express IL-10 receptor and angiogenic marker CD31 compared with the corresponding normal counterparts.

[Conclusion]

We continue to put effort in elucidating the pathogenic role of IL-10–secreting pDCs and developing strategy targeting the IL-10–IL-10 receptor pathway in the endometriotic milieu.

Graphical Abstract

Figure. The cartoon shows the effect and immune cell sources of IL-10 during the early and late stages of endometriosis. During the menstrual cycle and the early stage of endometriosis, retrograded endometrial cells or tissue enter peritoneal cavity. Lesion plasmacytoid dendritic cells (pDCs) may produce IL-10 in response to unwanted cells. Local IL-10 further promotes lesion growth by either suppressing anti-ectopic fragment immunity or stimulating angiogenesis. During the late stage of disease, the complex interaction among genetic factors, endogenous hormones, environmental endocrine disruptors (EEDs), and impaired immune surveillance leads to chronic inflammation. In the context of chronic inflammation in the peritoneal cavity, other immune cells can secrete IL-10 and other mediators to further promote the growth and maintenance of ectopic implants. [The figure is cited from Suen et al. 2019. (J Pathol. 2019 Dec;249(4):485-497)]

Main researcher Intro.

1.Dr. Jau-Ling Suen, the first author, at Kaohsiung Medical University study the role of innate immune cells in the pathogenesis of allergic asthma and endometriosis.

2.Dr. Eing-Mei Tsai, the corresponding author, a gynecologist and reproductive endocrinologist, at Kaohsiung Medical University Hospital. She has devoted in the mechanistic study in endometriosis.

3.Dr. Tzyh-Chyuan Hour, the equally contributed corresponding author, at Kaohsiung Medical University focus on the mechanistic study in prostate cancer and angiogenesis.

Author Email

jlsuen@kmu.edu.tw

Paper cited from: J Pathol. 2019 Dec;249(4):485-497. doi: 10.1002/path.5339.

Paper online website: https://pubmed.ncbi.nlm.nih.gov/31418859/