An important matter to revise: Immune system changes in endometriosis

Immunopathogenic mechanisms play pivotal roles in the disease development and progression in endometriosis

Key Points

Highlight:

• Immunologic mechanisms play vital roles in the pathogenesis of endometriosis with many factors being altered during the disease process. 

Importance:

• Alterations in the immune system seem to be responsible for many properties of endometriotic lesions such as adhesion, implantation, and invasion.
• Understanding these changes throughout the disease progression might provide new pathways to interfere in the treatment of the disease

What’s done here:

• This is a review study of the immunopathogenic pathways that are proven and/or thought to be responsible for disease development and progression in endometriosis.

Key results:

• Systemic and local changes are observed in both innate and humoral immune cell levels which include the macrophages, T- and B- lymphocytes, and NK cells.
• The phagocytic activities of macrophages are reduced in endometriosis.
• NK cell activity and cytotoxicity, and apoptosis have also been shown to be impaired.
• ICAM-1, VCAM-1, and the proinflammatory cytokines TNF-a, IL-6, and IL-8 are shown to be strongly expressed.
• Increased levels of VEGF cause angiogenic properties in the lesions.
•  The matrix metalloproteinases, in particular MMP-2 and MM-9, play essential roles in adhesion, invasion, and implantation.
• An increased number of activated CD20+ B-lymphocytes is seen resulting in the increased formation of new autoantigens.
• Treg lymphocytes are crucial in controlling and modulating the immune response in endometriotic cells.

Lay Summary

Endometriosis is a multifactorial disease with unclear and obscure pathogenetic mechanisms. In their review, Chopyak et al. revised the immunopathogenic pathways that are proven and/or thought to be responsible for disease development and progression. The article was published in the March 2022 issue of the Central European Journal of Immunology.

Alterations in the functions of the immune cells play an important role in endometriosis pathogenesis. Systemic and local changes are observed in both innate and humoral immune cell levels which include the macrophages, T- and B- lymphocytes, and NK cells. The peritoneal fluid is rich in macrophages and in endometriosis it was shown that improper polarization of macrophages may be causing tissue damage and immune dysfunction. The phagocytic activities of macrophages are also reduced in endometriosis by various proinflammatory molecules. NK cell activity and cytotoxicity, and apoptosis have also been shown to be impaired.

Humoral factors such as the adhesion molecules ICAM-1, VCAM-1, and the proinflammatory cytokines TNF-a, IL-6, and IL-8 are shown to be strongly expressed in endometriosis eliciting an invasive and proliferative milieu. Increased levels of VEGF cause angiogenic properties in the lesions. The matrix metalloproteinases, in particular MMP-2 and MM-9, play important roles in adhesion, invasion, and implantation. Adaptive immunity is also altered with diminished activities of CD8+ T cells and CD4+ T helper cells possibly caused by the upregulation of IL-4 and IL-10. An increased number of activated CD20+ B-lymphocytes is seen resulting in the increased formation of new autoantigens.

Besides progesterone resistance, there is a deficiency in the metabolism of E2 estrogen in endometriosis which causes activation of proliferation and inflammation in ectopic endometriotic tissues. Toll-like receptors are also known to play roles in the impairment of the immune response. Treg lymphocytes are very important in controlling and modulating the immune response in endometriotic cells.

Even though there are some studies focusing on the genetic alterations in the pathogenesis of endometriosis, a certain pathway is yet to be discovered. Metabolic factors such as Vitamin D and leptin have been among the latest research topics in endometriosis. The authors also talk about the hypothesis that endometriosis is an autoimmune disease with findings like increased autoantibodies or mutations in autoimmunity genes found in endometriosis patients.

They conclude by saying that the role of peritoneal inflammation in endometriosis should be elucidated and the factors of innate immunity should be studied further for the prognosis of infertility in women with endometriosis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/35600152/