Recirculating IL-1R2 Tregs fine-tune intrathymic Treg development under inflammatory conditions.
dc.contributor.author | Nikolouli, Eirini | |
dc.contributor.author | Elfaki, Yassin | |
dc.contributor.author | Herppich, Susanne | |
dc.contributor.author | Schelmbauer, Carsten | |
dc.contributor.author | Delacher, Michael | |
dc.contributor.author | Falk, Christine | |
dc.contributor.author | Mufazalov, Ilgiz A | |
dc.contributor.author | Waisman, Ari | |
dc.contributor.author | Feuerer, Markus | |
dc.contributor.author | Huehn, Jochen | |
dc.date.accessioned | 2020-02-19T11:53:05Z | |
dc.date.available | 2020-02-19T11:53:05Z | |
dc.date.issued | 2020-01-27 | |
dc.identifier.citation | Cell Mol Immunol. 2020 Jan 27. pii: 10.1038/s41423-019-0352-8. doi: 10.1038/s41423-019-0352-8. | en_US |
dc.identifier.issn | 2042-0226 | |
dc.identifier.pmid | 31988493 | |
dc.identifier.doi | 10.1038/s41423-019-0352-8 | |
dc.identifier.uri | http://hdl.handle.net/10033/622148 | |
dc.description.abstract | The 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.iso | en | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/648145 | en_US |
dc.rights | embargoedAccess | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | IL-1 system | en_US |
dc.subject | Inflammation | en_US |
dc.subject | Thymus | en_US |
dc.subject | Treg development | en_US |
dc.title | Recirculating IL-1R2 Tregs fine-tune intrathymic Treg development under inflammatory conditions. | en_US |
dc.type | Article | en_US |
dc.contributor.department | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. | en_US |
dc.identifier.journal | Cellular and molecular Immunology | en_US |
dc.source.journaltitle | Cellular & molecular immunology |