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Recirculating IL-1R2^(+) Tregs fine-tune intrathymic Treg development under inflammatory conditions

Cellular & Molecular Immunology 2021年第1期18卷 182-193页

作者： eirini nikolouli Yassin Elfaki Susanne Herppich Carsten Schelmbauer Michael Delacher Christine Falk Ilgiz A.Mufazalov Ari Waisman Markus Feuerer Jochen Huehn Department of Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-University MainzMainzGermany Regensburg Center for Interventional Immunology(RCI) Chair for ImmunologyUniversity Regensburg and University Hospital RegensburgRegensburgGermany Institute of Transplant Immunology Integrated Research and Treatment Center TransplantationIFB-TxHannover Medical SchoolHannoverGermany Hannover Medical School HannoverGermany

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 *** flow cytometric analysis of the thymocytes from Foxp3^(hCD2)xRAG1^(GFP) reporter mice revealed that the IL-1R2^(+)Tregs are mainly RAG1^(GFP-)and CCR6^(+)CCR7^(-),demonstrating that these Tregs are recirculating cells entering the thymus from the periphery and that they have an activated *** the spleen,the majority of IL-1R2^(+)Tregs express neuropilin-1(Nrp-1)and Helios,suggesting a thymic origin for these ***,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 *** 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 ***,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.

关键词： Thymus Treg development Inflammation IL-1 system

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