Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis

Interplay between Misplaced Müllerian-Derived Stem Cells and Peritoneal Immune Dysregulation in the Pathogenesis of Endometriosis

“…Therefore, cells that are expressing high FasL may cause apoptosis of surrounding lymphocytes and thereby escape from lymphocytes response. Like we argued in our previous work [73], PF of women with endometriosis may have a potential to induce apoptosis of cytotoxic T lymphocytes, directly or indirectly via stimulating endometriotic cells, and contribute to the survival of endometriosis. Besides cytotoxic T lymphocytes, characterized as CD8 + T cells, helper T cells or, namely, CD4 + T cells are further diminished in their activity in PF from patients with endometriosis, probably because PF homeostasis breakdown suppresses activation of helper T cells [72].…”

“…FasL (CD95L/CD178/Apo-1L) is a type II cell membrane protein (mFasL) which is inducibly expressed in lymphocytes and constitutively expressed in cells present in immune-privileged organs [94, 95]. We have previously reported [73] that Fas/FasL system is dysregulated progressively throughout the course of the disease, with the result that endometriotic cells do not undergo Fas/FasL-mediated apoptosis because they do not receive a death signal from PFMCs, thus implanting themselves and surviving outside of the uterus. Paradoxically, endometriotic cells become themselves capable of killing PFMCs, and this may allow their establishment in the peritoneum, which in turn becomes an immune privileged environment [96–99].…”

Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis

“…give answers as to why the eutopic plant develops resistance to the elimination by the immune system, demonstrating the altered function of macrophages and natural killer cells: that in the early stages of the disease there is a prevalence of pro-inflammatory cytokines (Th1 profile), whilst in late stages this changes to a Th2 profile [140]; that alterations of immune peritoneal exert an immunosuppressive effect on the activity of phagocytic and cytotoxic immune cells infiltrating the endometrial tissue, promoting immunoescaping, survival and growth of Page 19 of 40 endometrial cells [141][142][143][144]. Therapeutic strategies can be improved through the use of nonsteroidal anti-inflammatory drugs [145], combination oral contraceptives [146,147], progestin…”

Fas and Fas-Ligand in Eutopic and Ectopic Endometrium of Women With Endometriosis: The Possible Immune Privilege of Ectopic Endometrium

“…These data seem to suggest that the endometriotic tissue shows an immune privilege by the interaction of Fas-L produced by the epithelial cells and the Fas expressed on the leukocytes of the peritoneal cavity, which may lead to an increase in their rate of apoptosis and a substantial reduction in their scavenger activity. 26 In this way, the ectopic endometrial tissue may survive and proliferate avoiding the immunosurveillance of peritoneal leukocytes. Cellular membrane Fas-L could be transformed into the soluble form by the matrix metalloproteinases (MMPs), which are actively produced by the endometrium, especially MMP-2 and MMP-9.…”