A Disintegrin and Metalloproteinase 17 is required for ILC2 responses to IL-33
A Disintegrin and Metalloproteinase 17 is required for ILC2 responses to IL-33
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DOI：
10.1016/j.bbrc.2019.03.120
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发表时间：
2019-05-14
影响因子：
3.1
通讯作者：
Martin, Rebecca K.
中科院分区：
文献类型：
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作者：
Lownik, Joseph C.;Conrad, Daniel H.;Martin, Rebecca K.
第2组先天性淋巴样细胞（ILC 2）在启动2型免疫应答中起重要作用。已经鉴定了许多可以激活或抑制ILC 2功能的靶点，尽管在激活后诱导的负调节反馈途径已经显示在ILC 2中起作用。在这里，我们证明，从ILC 2的ADAM 17的损失导致IL-33的反应性的选择性缺陷，但不是IL-25的反应性。我们发现，IL-1 R2在IL-33激活的ILC 2中在转录和蛋白水平上均显著上调。我们还能够证明，ADAM 17调节ILC 2上的IL 1 R2水平在组成和激活诱导的方式。此外，IL 1 R2（+）ILC 2（ILC 2的独特子集）在IL-33刺激后具有减少的Il 5和Il 13转录物。总体而言，这些数据表明，IL 1 R2的表达可能作为激活诱导的负调节反馈机制，以降低ILC 2对IL-33的反应性。(C)2019爱思唯尔公司All rights reserved.
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, IL1 R2(+) 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. (C) 2019 Elsevier Inc. All rights reserved.