Center for Clinical and Translational Research, School of Medicine, Virginia Commonwealth University, Richmond, Virgini, 23298, USA.
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Biochem Biophys Res Commun. 2019 May 14;512(4):723-728. doi: 10.1016/j.bbrc.2019.03.120. Epub 2019 Mar 27.
Group 2 innate lymphoid cells (ILC2s) play an important role in the initiation of type-2 immune responses. Numerous targets have been identified that may activate or repress ILC2 function, though few negative regulatory feedback pathways induced upon activation have been shown to be operative in ILC2s. Here we demonstrate that loss of ADAM17 from ILC2s results in a selective defect in IL-33 responsiveness, but not IL-25 responsiveness. We find that IL1R2 is significantly upregulated at both the transcript and protein level in IL-33 activated ILC2s. We are also able to demonstrate that ADAM17 regulates IL1R2 levels on ILC2s in both a constitutive and activation induced manner. Additionally, IL1R2 ILC2s, a unique subset of ILC2s, have decreased Il5 and Il13 transcripts following IL-33 stimulation. Overall, these data suggest that the expression of IL1R2 may act as an activation-induced negative regulatory feedback mechanism to decrease ILC2 responsiveness to IL-33.
2 型固有淋巴细胞（ILC2s）在启动 2 型免疫反应中发挥重要作用。已经鉴定出许多可能激活或抑制 ILC2 功能的靶标，但在 ILC2 中显示出的激活后诱导的负反馈调节途径很少。在这里，我们证明 ILC2 中缺失 ADAM17 会导致对 IL-33 的反应性选择性缺陷，但对 IL-25 的反应性没有缺陷。我们发现，IL1R2 在 IL-33 激活的 ILC2s 中无论是在转录水平还是蛋白水平都显著上调。我们还能够证明 ADAM17 以组成型和激活诱导的方式调节 ILC2s 上的 IL1R2 水平。此外，IL1R2 ILC2s，即 ILC2s 的一个独特亚群，在受到 IL-33 刺激后，其 Il5 和 Il13 转录物减少。总的来说，这些数据表明，IL1R2 的表达可能作为一种激活诱导的负反馈调节机制，降低 ILC2 对 IL-33 的反应性。
