Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Elife. 2020 Jul 20;9:e58213. doi: 10.7554/eLife.58213.
Foxp3+ regulatory T cells (Tregs) are potent suppressor cells, essential for the maintenance of immune homeostasis. Most Tregs develop in the thymus and are then released into the immune periphery. However, some Tregs populate the thymus and constitute a major subset of yet poorly understood cells. Here we describe a subset of thymus recirculating IL18R Tregs with molecular characteristics highly reminiscent of tissue-resident effector Tregs. Moreover, we show that IL18R Tregs are endowed with higher capacity to populate the thymus than their IL18R or IL18R counterparts, highlighting the key role of IL18R in this process. Finally, we demonstrate that IL18 signaling is critical for the induction of the key thymus-homing chemokine receptor - CCR6 on Tregs. Collectively, this study provides a detailed characterization of the mature Treg subsets in the mouse thymus and identifies a key role of IL18 signaling in controlling the CCR6-CCL20-dependent migration of Tregs into the thymus.
Foxp3+ 调节性 T 细胞（Tregs）是强有力的抑制性细胞，对于维持免疫稳态至关重要。大多数 Tregs 在胸腺中发育，然后释放到免疫外周。然而，一些 Tregs 存在于胸腺中，构成了一个尚未充分了解的主要亚群。在这里，我们描述了一种具有分子特征的胸腺再循环 IL18R Tregs 亚群，这些特征高度类似于组织驻留效应性 Tregs。此外，我们表明，IL18R Tregs 比其 IL18R 或 IL18R 对应物更有能力在胸腺中定植，突出了 IL18R 在这个过程中的关键作用。最后，我们证明了 IL18 信号对于诱导 Tregs 上关键的胸腺归巢趋化因子受体 CCR6 的表达至关重要。总之，这项研究提供了对小鼠胸腺中成熟 Treg 亚群的详细特征描述，并确定了 IL18 信号在控制 Tregs 向胸腺中 CCR6-CCL20 依赖性迁移中的关键作用。
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