Natural Killer Cells: Key Players in Endometriosis

Thiruchelvam, Uma; Wingfield, Mary; O’Farrelly, Cliona

doi:10.1111/aji.12408

Cited by 96 publications

(95 citation statements)

References 104 publications

(190 reference statements)

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“…Consequently, decreased expression of both SIGIRR and CEACAM-1 genes in ectopic tissues may explain the dysregulated inflammatory cytokine elevation and T-cell activation observed in endometriosis patients. Furthermore, decreased expression of NFIL3 (32), IL15 (33), and GNLY (34) in ectopic lesions support diminished cytotoxicity of NK and CD8+ T cells in women with endometriosis toward autologous endometrial fragments (35, 36). The expression of genes involved in signaling pathways, including TRAF4, MAPK1 , and DUSP4 , were significantly decreased in expression in ectopic tissues compared with control endometrium.…”

Section: Discussionmentioning

confidence: 83%

Immune-inflammation gene signatures in endometriosis patients

Ahn

Khalaj

Young

et al. 2016

Fertility and Sterility

140

102

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Objective To determine if the molecular profiles of endometriotic lesions contain informative measures of inflammation and immune dysfunction that may contribute to better understanding of the interplay between immune dysfunction and inflammation and their contribution to endometriosis pathogenesis. Design Immune and inflammation transcriptomic analysis with the use of the Nanostring nCounter GX Human Immunology V2 platform (579 human immune and inflammation–related genes and 15 housekeeping genes). Setting Academic university and teaching hospital. Intervention(s) None. Patient(s) Stage III–IV endometriosis patients with infertility (n = 8) and fertile disease-free control women undergoing tubal ligation (n = 8). Menstrual stage was matched to secretory phase in all participants. Main Outcome Measure(s) Immune and inflammation transcriptomics quantification from ectopic endometriotic lesions and matched eutopic endometrium from patients. Endometria of fertile women served as control subjects. Result(s) Our results displayed endometriotic lesions as molecularly distinct entities compared with eutopic endometrium and endometrium of control samples; 396 out of 579 screened immune and inflammation–related genes were significantly different in ectopic tissues compared with control endometrium. Most importantly, eutopic endometrium of the patients displayed a unique molecular profile compared with the control endometrium (91/579 genes were significantly different), particularly of genes involved in regulation of cell apoptosis and decidualization. Conclusion(s) We characterize differential expression of immune-inflammation genes in endometriosis patients, and show molecular distinction of eutopic endometrium of patients compared with control fertile women.

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Section: Discussionmentioning

confidence: 83%

Immune-inflammation gene signatures in endometriosis patients

Ahn

Khalaj

Young

et al. 2016

Fertility and Sterility

140

102

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“…With regard to endometriosis, the cytotoxic function is reduced in peripheral and peritoneal NK cells. [53][54][55][56][57] Due to diminished cytotoxicity, retrograde endometrial cells are prone to survive in the peritoneal cavity, which results in the development of endometriosis. Factors controlling NK cell function have not been thoroughly investigated; however, several studies have shown that IL-6, 57 IL-15, 58 and transforming growth factor-β1 59 suppress NK cell cytotoxic activity.…”

Section: Reduced Nk Cell Cytotoxic Activity In Endometriosismentioning

confidence: 99%

“…With regard to endometriosis, the cytotoxic function is reduced in peripheral and peritoneal NK cells . Due to diminished cytotoxicity, retrograde endometrial cells are prone to survive in the peritoneal cavity, which results in the development of endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Involvement of immune cells in the pathogenesis of endometriosis

Izumi

Koga

Takamura

et al. 2018

J of Obstet and Gynaecol

135

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Endometriosis is characterized by the implantation and growth of endometriotic tissues outside the uterus. It is widely accepted the theory that endometriosis is caused by the implantation of endometrial tissue from retrograde menstruation; however, retrograde menstruation occurs in almost all women and other factors are required for the establishment of endometriosis, such as cell survival, cell invasion, angiogenesis, and cell growth. Immune factors in the local environment may, therefore, contribute to the formation and progression of endometriosis. Current evidence supports the involvement of immune cells in the pathogenesis of endometriosis. Peritoneal neutrophils and macrophages secrete biochemical factors that help endometriotic cell growth and invasion, and angiogenesis. Peritoneal macrophages and NK cells in endometriosis have limited capability of eliminating endometrial cells in the peritoneal cavity. An imbalance of T cell subsets leads to aberrant cytokine secretions and inflammation that results in the growth of endometriosis lesions. It is still uncertain whether these immune cells have a role in the initial cause and/or stimulate actions that enhance disease; however, in either case, modulating the actions of these cells may prevent initiation or disease progression. Further studies are needed to deepen the understanding of the pathology of endometriosis and to develop novel management approaches of benefit to women suffering from this disease.

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“…NK cells have a decreased expression of inhibitory KIRs, including KIR3DL1 (also known as NKB1) and KIR2DL3 (also known as GL183), on their surface and have enhanced cytotoxic functions. In endometriosis, peripheral NK cells and peritoneal NK cells exhibit an increased expression of KIRs and have reduced levels of cytotoxicity (63). Endometriotic cells develop several strategies to escape immune surveillance to avoid attack from the immune system.…”

Section: Functional Pathways Of Adenomyosis Candidate Genesmentioning

confidence: 99%