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^hCD2xRAG1^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-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.

绝大多数 Foxp3 ⁺调节性 T 细胞 (Tregs) 是在胸腺中产生的，已知一些因素，如细胞因子和独特的胸腺抗原呈递细胞，有助于这些胸腺衍生的 Tregs (tTregs) 的发育。^{在这里，我们报告了胸腺内存在 Foxp3 +} Tregs的特定子集，其特征是 IL-1R2 的表达，IL-1R2 是炎性细胞因子 IL-1 的诱饵受体。^{Foxp3 hCD2} xRAG1 ^GFP报告小鼠胸腺细胞的详细流式细胞术分析显示，IL-1R2 ⁺ Tregs 主要是 RAG1 ^GFP-和 CCR6 ⁺ CCR7 ^-，证明这些 Treg 是从外周进入胸腺的循环细胞，并且它们具有激活的表型。在脾脏中，大多数 IL-1R2 ⁺ Tregs 表达 neuropilin-1 (Nrp-1) 和 Helios，表明这些 Tregs 的胸腺起源。有趣的是，在所有研究的组织中，在胸腺中观察到最高频率的 IL-1R2 ⁺ Tregs，表明胸腺优先募集该 Treg 子集。使用胎儿胸腺器官培养物 (FTOC)，我们证明了增加浓度的外源性 IL-1β 阻止了胸腺内 Treg 的发育，导致 CD25 ⁺ Foxp3 ⁺ tTregs 的频率降低和 CD25 ⁺ Foxp3的积累^-Treg 前体。有趣的是，向重新聚集的胸腺器官培养物 (RTOC) 添加 IL-1R2 ⁺ Tregs 而不是 IL-1R2 ^- Tregs，消除了 IL-1β 介导的阻断，证明这些再循环的 IL-1R2 ⁺ Tregs 可以淬灭 IL-1在胸腺中发出信号，从而即使在炎症条件下也能维持胸腺 Treg 的发育。