TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.

<h4>Background</h4>TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implant...

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Autores principales: Marie Petitbarat, Mona Rahmati, Valérie Sérazin, Sylvie Dubanchet, Corinne Morvan, Robert Wainer, Philippe de Mazancourt, Gérard Chaouat, Jean-Michel Foidart, Carine Munaut, Nathalie Lédée
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spelling oai:doaj.org-article:5705640e236f4589842bfc1a521a9b7d2021-11-18T07:00:40ZTWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.1932-620310.1371/journal.pone.0014497https://doaj.org/article/5705640e236f4589842bfc1a521a9b7d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21249128/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity.<h4>Methodology/principal findings</h4>Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions.<h4>Conclusions/significance</h4>TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human.Marie PetitbaratMona RahmatiValérie SérazinSylvie DubanchetCorinne MorvanRobert WainerPhilippe de MazancourtGérard ChaouatJean-Michel FoidartCarine MunautNathalie LédéePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14497 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marie Petitbarat
Mona Rahmati
Valérie Sérazin
Sylvie Dubanchet
Corinne Morvan
Robert Wainer
Philippe de Mazancourt
Gérard Chaouat
Jean-Michel Foidart
Carine Munaut
Nathalie Lédée
TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
description <h4>Background</h4>TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity.<h4>Methodology/principal findings</h4>Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions.<h4>Conclusions/significance</h4>TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human.
format article
author Marie Petitbarat
Mona Rahmati
Valérie Sérazin
Sylvie Dubanchet
Corinne Morvan
Robert Wainer
Philippe de Mazancourt
Gérard Chaouat
Jean-Michel Foidart
Carine Munaut
Nathalie Lédée
author_facet Marie Petitbarat
Mona Rahmati
Valérie Sérazin
Sylvie Dubanchet
Corinne Morvan
Robert Wainer
Philippe de Mazancourt
Gérard Chaouat
Jean-Michel Foidart
Carine Munaut
Nathalie Lédée
author_sort Marie Petitbarat
title TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
title_short TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
title_full TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
title_fullStr TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
title_full_unstemmed TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers.
title_sort tweak appears as a modulator of endometrial il-18 related cytotoxic activity of uterine natural killers.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/5705640e236f4589842bfc1a521a9b7d
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