Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/526 |
Resumo: | Implantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment. |
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Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantationregulatory T cellsimplantationpregnancyfibrosisinflammationImplantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment.DFG grants: (ZE526/4-2, SFB854TP7), Wilhelm Sander Stiftung Germany grant: (2009.022.1), Helmholtz Alliance for Immunotherapy, FCT, Medical Faculty Otto-von-Guericke University PhD grant.Frontiers Research FoundationARCAZenclussen, Ana ClaudiaHämmerling, Günter J.Tadokoro, Carlos EduardoReichardt, PeterThuere, CatharinaLinzke, NadjaKühnle, Marie-CristineSchumacher, AnneTeles, Ana2015-11-25T17:03:11Z2013-06-202013-06-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/526engTeles A, Schumacher A, Kühnle M-C, Linzke N, Thuere C, Reichardt P, Tadokoro CE, Hämmerling GJ and Zenclussen AC (2013) Control of uterine microenvironment by Foxp3+ cells facilitates embryo implantation. Front. Immunol. 4:158. doi: 10.3389/fimmu.2013.00158 Günter J. Hämmerling and Ana Claudia Zenclussen are co-senior authors.10.3389/fimmu.2013.00158info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:34:53Zoai:arca.igc.gulbenkian.pt:10400.7/526Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:46.909888Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
title |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
spellingShingle |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation Zenclussen, Ana Claudia regulatory T cells implantation pregnancy fibrosis inflammation |
title_short |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
title_full |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
title_fullStr |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
title_full_unstemmed |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
title_sort |
Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation |
author |
Zenclussen, Ana Claudia |
author_facet |
Zenclussen, Ana Claudia Hämmerling, Günter J. Tadokoro, Carlos Eduardo Reichardt, Peter Thuere, Catharina Linzke, Nadja Kühnle, Marie-Cristine Schumacher, Anne Teles, Ana |
author_role |
author |
author2 |
Hämmerling, Günter J. Tadokoro, Carlos Eduardo Reichardt, Peter Thuere, Catharina Linzke, Nadja Kühnle, Marie-Cristine Schumacher, Anne Teles, Ana |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Zenclussen, Ana Claudia Hämmerling, Günter J. Tadokoro, Carlos Eduardo Reichardt, Peter Thuere, Catharina Linzke, Nadja Kühnle, Marie-Cristine Schumacher, Anne Teles, Ana |
dc.subject.por.fl_str_mv |
regulatory T cells implantation pregnancy fibrosis inflammation |
topic |
regulatory T cells implantation pregnancy fibrosis inflammation |
description |
Implantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-06-20 2013-06-20T00:00:00Z 2015-11-25T17:03:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/526 |
url |
http://hdl.handle.net/10400.7/526 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Teles A, Schumacher A, Kühnle M-C, Linzke N, Thuere C, Reichardt P, Tadokoro CE, Hämmerling GJ and Zenclussen AC (2013) Control of uterine microenvironment by Foxp3+ cells facilitates embryo implantation. Front. Immunol. 4:158. doi: 10.3389/fimmu.2013.00158 Günter J. Hämmerling and Ana Claudia Zenclussen are co-senior authors. 10.3389/fimmu.2013.00158 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Research Foundation |
publisher.none.fl_str_mv |
Frontiers Research Foundation |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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