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dc.contributor.authorŁyszkiewicz, Marcin
dc.contributor.authorWinter, Samantha J
dc.contributor.authorWitzlau, Katrin
dc.contributor.authorFöhse, Lisa
dc.contributor.authorBrownlie, Rebecca
dc.contributor.authorPuchałka, Jacek
dc.contributor.authorVerheyden, Nikita A
dc.contributor.authorKunze-Schumacher, Heike
dc.contributor.authorImelmann, Esther
dc.contributor.authorBlume, Jonas
dc.contributor.authorRaha, Solaiman
dc.contributor.authorSekiya, Takashi
dc.contributor.authorYoshimura, Akihiko
dc.contributor.authorFrueh, Jochen T
dc.contributor.authorUllrich, Evelyn
dc.contributor.authorHuehn, Jochen
dc.contributor.authorWeiss, Siegfried
dc.contributor.authorGutierrez, Maximiliano G
dc.contributor.authorPrinz, Immo
dc.contributor.authorZamoyska, Rose
dc.contributor.authorZiętara, Natalia
dc.contributor.authorKrueger, Andreas
dc.date.accessioned2019-03-28T12:18:39Z
dc.date.available2019-03-28T12:18:39Z
dc.date.issued2019-03-01
dc.identifier.issn1545-7885
dc.identifier.pmid30856173
dc.identifier.doi10.1371/journal.pbio.2006716
dc.identifier.urihttp://hdl.handle.net/10033/621731
dc.description.abstractThe interdependence of selective cues during development of regulatory T cells (Treg cells) in the thymus and their suppressive function remains incompletely understood. Here, we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-181a-1 and miR-181b-1 (miR-181a/b-1) during late T-cell development with very high levels of expression during thymocyte selection, followed by massive down-regulation in the periphery. Loss of miR-181a/b-1 resulted in inefficient de novo generation of Treg cells in the thymus but simultaneously permitted homeostatic expansion in the periphery in the absence of competition. Modulation of T-cell receptor (TCR) signal strength in vivo indicated that miR-181a/b-1 controlled Treg-cell formation via establishing adequate signaling thresholds. Unexpectedly, miR-181a/b-1-deficient Treg cells displayed elevated suppressive capacity in vivo, in line with elevated levels of cytotoxic T-lymphocyte-associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral Treg cells. Therefore, we propose that intrathymic miR-181a/b-1 controls development of Treg cells and imposes a developmental legacy on their peripheral function.en_US
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titlemiR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany.en_US
dc.identifier.journalPLOS Biologyen_US
refterms.dateFOA2019-03-28T12:50:11Z
dc.source.journaltitlePLoS biology


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