2. 子宮内膜症発症メカニズムにおける逆流経血とその免疫学的監視機構(シンポジウム3(生殖・女性ヘルスケア) 子宮内膜症の病因・病態解明と治療戦略,第66回日本産科婦人科学会・学術講演会)

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  • 2. Decreased Immunosurveillance System in Peritoneal Cavity to Retrograde Menstruation in Women with Endometriosis

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Impaired peritoneal natural killer (NK) activity and function of macrophages in women with endometriosis is thought to promote implantation and progression of endometrial tissue in accord with Sampson's hypothesis. However, mechanisms responsible for decreased NK cell activity and the antigens recognized by NK cells are not clear. Furthermore, the mechanism of macrophage dysfunction is not clear. Decreased NK cell activity in peripheral blood (PB) and peritoneal fluid (PF) from women with endometriosis first was reported by Oosterlynck et al. and subsequent investigators have described functional depression of NK cells in this disorder. Decreased NK cell activity in women with endometriosis is thought to permit implantation of endometrial tissue in the manner of a tissue graft, but the mechanisms that suppress NK cell activity in endometriosis are not clear. Furthermore, we found the decreased macrophage function, in particular antigen presentation. Decreased antigen presentation by peritoneal macrophage may also permit implantation of endometrial tissue in the peritoneal cavity. We focused on the HLA-G, a ligand of NK receptors, expression and its menstrual cycle changes by eutopic endometrium. Interestingly, HLA-G expression was identified on eutopic endometrium only in the menstrual phase but not in proliferative or secretory phases. Furthermore, HLA-G-expressing cells were also detected in peritoneal fluid during the menstrual period. During retrograde menstruation, HLA-G-expressing endometrial tissue may enter into the peritoneal cavity, and may be diminished by immunosurveillance system. Although peritoneal NK cells and macrophages play an important role in this system, but impairment of NK cytotoxicity via HLA-G and decreased macrophage antigen presentation may allow peritoneal endometrial cell survival and its implantation. The impairment of its physiological immunosurveillance system in particular NK cell and macrophage function may favor the endometrial cell survive and implantation and trigger of the onset of endometriosis. Further investigation of the molecular mechanisms leading to induction of antigens during menstruation and the function of immunocompetent responder cells in the PF may contribute to a better understanding of the pathogenesis of endometriosis.

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