Regulatory T cells (Tregs) have been shown to attenuate the development and progression of atherosclerosis; however, the exact mechanism is still unclear. In our study, Tregs were adoptively transferred into ApoE^−/− mice, and type 2 innate lymphoid cells (ILC2s) were expanded by the IL-2/Jes6-1 complex or depleted by anti-CD90.2 mAb in ApoE^−/-Rag1^−/− mice to study their effects on atherosclerosis. Then, Tregs were cocultured with ILC2s in vitro to analyze ILC2s number and IL-13 production. In vivo, ApoE^−/-Rag1^−/− mice were treated with activated Tregs with or without anti-CD90.2 mAb to explore whether Tregs reduced atherosclerosis through ILC2s. Finally, neutralizing antibodies and Transwell assay were used to investigate how Tregs regulate ILC2s. Our results show that both Tregs and ILC2s reduce atherosclerosis lesions and macrophage infiltration. Moreover, Tregs effectively expanded the number of ILC2s and increased their production of IL-13 in vivo and in vitro. Furthermore, the reductions in plaque size and macrophage infiltration by Tregs were partly reversed by anti-CD90.2 mAb. Mechanistically, our data reveal that IL-10, TGF-β and cell-cell contacts are required for Tregs-ILC2s regulation. These results show that Tregs may play a partial protective role against atherosclerosis by expanding the number of ILC2s and consequently increasing IL-13 production.

调节性 T 细胞 (Tregs) 已被证明可以减轻动脉粥样硬化的发展和进展；然而，确切的机制仍不清楚。在我们的研究中，Tregs 被过继转移到 ApoE ^-/-小鼠中，2 型先天淋巴细胞 (ILC2s) 被 IL-2/Jes6-1 复合物扩增或被 ApoE ^{-/- 中的}抗 CD90.2 mAb 耗尽Rag1 ^-/-小鼠研究它们对动脉粥样硬化的影响。然后，在体外将Tregs 与 ILC2s 共培养以分析 ILC2s 的数量和 IL-13 的产生。在体内， ApoE ^-/- Rag1 ^-/-用有或没有抗 CD90.2 mAb 的活化 Tregs 治疗小鼠，以探索 Tregs 是否通过 ILC2 减少动脉粥样硬化。最后，使用中和抗体和 Transwell 测定来研究 Tregs 如何调节 ILC2。我们的结果表明 Tregs 和 ILC2s 都减少了动脉粥样硬化病变和巨噬细胞浸润。此外，Tregs 有效地增加了 ILC2 的数量并增加了它们在体内和体外的 IL-13 的产生. 此外，抗 CD90.2 mAb 部分逆转了 Treg 对斑块大小和巨噬细胞浸润的减少。从机制上讲，我们的数据显示 Tregs-ILC2s 调节需要 IL-10、TGF-β 和细胞 - 细胞接触。这些结果表明，Tregs 可能通过增加 ILC2 的数量并因此增加 IL-13 的产生而对动脉粥样硬化发挥部分保护作用。