Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/66387
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dc.contributor.authorGuerin, L.en
dc.contributor.authorMoldenhauer, L.en
dc.contributor.authorPrins, J.en
dc.contributor.authorBromfield, J.en
dc.contributor.authorHayball, J.en
dc.contributor.authorRobertson, S.en
dc.date.issued2011en
dc.identifier.citationBiology of Reproduction, 2011; 85(2):397-408en
dc.identifier.issn0006-3363en
dc.identifier.issn1529-7268en
dc.identifier.urihttp://hdl.handle.net/2440/66387-
dc.description.abstractRegulatory T (Treg) cells facilitate maternal immune tolerance of the semiallogeneic conceptus in early pregnancy, but the origin and regulation of these cells at embryo implantation is unclear. During the preimplantation period, factors in the seminal fluid delivered at coitus cause expansion of a CD4+CD25+ putative Treg cell population in the para-aortic lymph nodes draining the uterus. Using flow cytometry, immunohistochemistry, and real-time quantitative PCR (qPCR) for the signature Treg cell transcription factor FOXP3, we confirmed the identity of the expanded lymph node population as FOXP3+ Treg cells and showed that this is accompanied by a comparable increase in the uterus of FOXP3+ Treg cells and expression of Foxp3 mRNA by Day 3.5 postcoitum. Seminal plasma was necessary for uterine Treg cell accumulation, as mating with seminal vesicle-deficient males failed to elicit an increase in uterine Treg cells. Furthermore seminal fluid induced expression of mRNA encoding the Treg chemokine CCL19 (MIP3beta), which acts through the CCR7 receptor to regulate Treg cell recruitment and retention in peripheral tissues. Glandular and luminal epithelial cells were identified as the major cellular origins of uterine CCL19, and exposure to both seminal plasma and sperm was required for maximum expression. Together, these results indicate that Treg cells accumulate in the uterus prior to embryo implantation and that seminal fluid is a key regulator of the uterine Treg cell population, operating by both increasing the pool of available Treg cells and promoting their CCL19-mediated recruitment from the circulation into the implantation site.en
dc.description.statementofresponsibilityLeigh R. Guerin, Lachlan M. Moldenhauer, Jelmer R. Prins, John J. Bromfield, John D. Hayball and Sarah A. Robertsonen
dc.language.isoenen
dc.publisherSoc Study Reproductionen
dc.rights© 2011 by the Society for the Study of Reproduction, Inc. Copyright © 2011 by the Biology of Reproductionen
dc.subjectcytokines; immunology; pregnancy; regulatory T cells; seminal fluid; tolerance; uterusen
dc.titleSeminal fluid regulates accumulation of FOXP3(+) regulatory T cells in the preimplantation mouse uterus through expanding the FOXP3(+) cell pool and CCL19-mediated recruitmenten
dc.typeJournal articleen
dc.identifier.rmid0020111260en
dc.identifier.doi10.1095/biolreprod.110.088591en
dc.identifier.pubid28397-
pubs.library.collectionObstetrics and Gynaecology publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidHayball, J. [0000-0002-3089-4506]en
dc.identifier.orcidRobertson, S. [0000-0002-9967-0084]en
Appears in Collections:Obstetrics and Gynaecology publications

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