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Endometriotic tissu...
Endometriotic tissue-derived exosomes downregulate NKG2D-mediated cytotoxicity and promote apoptosis : mechanisms for survival of endometriotic tissue at ectopic sites
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- Björk, Emma, 1977- (författare)
- Umeå universitet,Obstetrik och gynekologi,Immunologi/immunkemi,Division of Obstetrics and Gynecology/Örnsköldsvik Hospital, Örnsköldsvik, Sweden,Ulrika Ottander
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- Israelsson, Pernilla (författare)
- Umeå universitet,Institutionen för diagnostik och intervention,Onkologi
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- Nagaev, Ivan (författare)
- Umeå universitet,Klinisk immunologi
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visa fler...
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- Nagaeva, Olga, 1958- (författare)
- Umeå universitet,Klinisk immunologi
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- Lundin, Eva (författare)
- Umeå universitet,Patologi
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- Ottander, Ulrika (författare)
- Umeå universitet,Immunologi/immunkemi
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visa färre...
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(creator_code:org_t)
- ISBN 9789180704090
- 2024
- Engelska 82 + 4 papers s.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Endometriosis, affecting 10% of women, is defined as implantation, survival, and growth of endometriumlike/endometriotic tissue outside the uterine cavity, causing inflammation, infertility, pain andsusceptibility to ovarian cancer. Despite extensive studies, its etiology and pathogenesis are poorlyunderstood and largely unknown. The prevailing view is that the immune system of endometriosispatients fails to clear ectopically disseminated endometrium from retrograde menstruation. Exosomes aresmall extracellular vesicles that exhibit immunomodulatory properties. We studied the role ofendometriotic tissue-secreted exosomes in the pathophysiology of endometriosis. Two exosome-mediatedmechanisms known to impair the immune response were investigated: 1) downregulation of NKG2Dmediatedcytotoxicity and 2) FasL- and TRAIL-induced apoptosis of activated immune cells. We showedthat secreted endometriotic exosomes isolated from supernatants of short-term explant cultures carry theNKG2D ligands MICA/B and ULBP1-3; and the proapoptotic molecules FasL and TRAIL on theirsurface, i.e. signature molecules of exosome-mediated immune suppression. Acting as decoys, theseexosomes downregulate the NKG2D receptor, impair NKG2D-mediated cytotoxicity and induce apoptosisof activated PBMC and Jurkat cells through the FasL- and TRAIL pathway. The secreted endometrioticexosomes create an immunosuppressive gradient at the ectopic site, forming a “protective shield” aroundthe endometriotic lesions. This gradient guards the endometriotic lesions against clearance by a cytotoxicattack and creates immunologic privilege by induction of apoptosis in activated immune cells. Takentogether, our results provide a plausible, exosome-based mechanistic explanation for the immunedysfunction and the compromised immune surveillance in endometriosis and contribute with novelinsights into the pathogenesis of this enigmatic disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- endometriosis
- exosomes
- NKG2D receptor
- MICA/B
- ULBP1-3
- FasL
- TRAIL
- obstetrik och gynekologi
- Obstetrics and Gynaecology
- immunologi
- Immunology
- Pathology
- patologi
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)
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