Immunopathogenesis of endometriosis-a novel look at an old problem

This review aims to cast a look at endometriosis as a chronic and progressive gynecological disease. Endometriosis-affected tissues show a variety of pathologic features: alterations in cell growth, apoptosis, activation, angiogenesis, cell adhesion, and cytokine production. Fresh endometriotic lesions are associated with induction of an inflammatory reaction represented by overproduction of prostaglandins (PGE2), metalloproteinases (MMP-2, -3, -9), cytokines (IL-113, IL-8, IFN-??, TNF-??, MCP-1 and MIF) and adhesive molecules (ICAM-1, VCAM-1) and activation of synthesis of reactive oxygen and nitrogen species. The inflammatory process may lead to defective folliculogenesis by an altered follicular milieu. An increase in the number and change in function of macrophages, T- and B-lymphocytes and reduction of NK cells have been reported. Treg lymphocytes are known to play an extremely important role in controlling and modulating changes in the aberrant immune response in endometriosis. Dysregulation of the immune system results in both increased progression of endometriosis and its severity. In inflammatory conditions the immune cells provide immune defense at the local level - in peritoneal fluid - and could further cause: 1) a decrease of the number of NK CD16+ cells with expression of KIRs and an increase of NK CD57+; 2) increased numbers of CD8+ cells and CD11b- immature dendritic cells; 3) an increase of FoxP3 expression in the regulatory T cell (Treg) population; 4) an increase of macrophages activating T- and B-lymphocytes leading to elevated synthesis of cytokines and/or autoantibodies. We may conclude that endometriosis resembles an immunodependent disease with the autoimmune background and breakdown of immunosuppressive mechanisms. Further immunological investigations may open a new avenue to discover innovative immunomodulatory treatments of endometriosis.

Automated summary

Endometriosis is a chronic and progressive gynecological disease characterized by alterations in cell growth, inflammatory reactions, changes in immune cell numbers and functions, and immunoregulation. Regulatory T lymphocytes play a crucial role in controlling the immune response, while dysregulation of the immune system may lead to disease progression and severity.