Nikolouli, Eirini and Elfaki, Yassin and Herppich, Susanne and Schelmbauer, Carsten and Delacher, Michael and Falk, Christine and Mufazalov, Ilgiz A. and Waisman, Ari and Feuerer, Markus and Huehn, Jochen (2021) Recirculating IL-1R2(+) Tregs fine-tune intrathymic Treg development under inflammatory conditions. CELLULAR & MOLECULAR IMMUNOLOGY, 18 (1). pp. 182-193. ISSN 1672-7681, 2042-0226
Full text not available from this repository. (Request a copy)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 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 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-1 beta 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-1 beta-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; IL-1 RECEPTOR; B-CELLS; DENDRITIC CELLS; EXPRESSION; THYMUS; GENERATION; DIFFERENTIATION; AUTOIMMUNITY; ACTIVATION; Thymus; Treg development; Inflammation; IL-1 system |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Feb 2022 06:02 |
| Last Modified: | 28 Feb 2022 06:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45316 |
Actions (login required)
 |
View Item |
