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dc.contributor.authorNikolouli, Eirini
dc.contributor.authorElfaki, Yassin
dc.contributor.authorHerppich, Susanne
dc.contributor.authorSchelmbauer, Carsten
dc.contributor.authorDelacher, Michael
dc.contributor.authorFalk, Christine
dc.contributor.authorMufazalov, Ilgiz A
dc.contributor.authorWaisman, Ari
dc.contributor.authorFeuerer, Markus
dc.contributor.authorHuehn, Jochen
dc.date.accessioned2020-02-19T11:53:05Z
dc.date.available2020-02-19T11:53:05Z
dc.date.issued2020-01-27
dc.identifier.citationCell Mol Immunol. 2020 Jan 27. pii: 10.1038/s41423-019-0352-8. doi: 10.1038/s41423-019-0352-8.en_US
dc.identifier.issn2042-0226
dc.identifier.pmid31988493
dc.identifier.doi10.1038/s41423-019-0352-8
dc.identifier.urihttp://hdl.handle.net/10033/622148
dc.description.abstractThe vast majority of Foxp3+ regulatory T cells (Tregs) are generated in the thymus, and several factors, such as cytokines and unique thymic antigen-presenting cells, are known to contribute to the development of these thymus-derived Tregs (tTregs). Here, we report the existence of a specific subset of Foxp3+ Tregs within the thymus that is characterized by the expression of IL-1R2, which is a decoy receptor for the inflammatory cytokine IL-1. Detailed flow cytometric analysis of the thymocytes from Foxp3hCD2xRAG1GFP reporter mice revealed that the IL-1R2+ Tregs are mainly RAG1GFP- and CCR6+CCR7-, demonstrating that these Tregs are recirculating cells entering the thymus from the periphery and that they have an activated phenotype. In the spleen, the majority of IL-1R2+ Tregs express neuropilin-1 (Nrp-1) and Helios, suggesting a thymic origin for these Tregs. Interestingly, among all tissues studied, the highest frequency of IL-1R2+ Tregs was observed in the thymus, indicating preferential recruitment of this Treg subset by the thymus. Using fetal thymic organ cultures (FTOCs), we demonstrated that increased concentrations of exogenous IL-1β blocked intrathymic Treg development, resulting in a decreased frequency of CD25+Foxp3+ tTregs and an accumulation of CD25+Foxp3- Treg precursors. Interestingly, the addition of IL-1R2+ Tregs, but not IL-1R2- Tregs, to reaggregated thymic organ cultures (RTOCs) abrogated the IL-1β-mediated blockade, demonstrating that these recirculating IL-1R2+ Tregs can quench IL-1 signaling in the thymus and thereby maintain thymic Treg development even under inflammatory conditions.en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/648145en_US
dc.rightsembargoedAccessen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectIL-1 systemen_US
dc.subjectInflammationen_US
dc.subjectThymusen_US
dc.subjectTreg developmenten_US
dc.titleRecirculating IL-1R2 Tregs fine-tune intrathymic Treg development under inflammatory conditions.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalCellular and molecular Immunologyen_US
dc.source.journaltitleCellular & molecular immunology


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