IL-15 sustains IL-7R-independent ILC2 and ILC3 development.
IL-15 sustains IL-7R-independent ILC2 and ILC3 development.
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DOI：
10.1038/ncomms14601
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发表时间：
2017-03-31
影响因子：
16.6
通讯作者：
Colonna M
中科院分区：
文献类型：
--
作者：
Robinette ML;Bando JK;Song W;Ulland TK;Gilfillan S;Colonna M
维持组织驻留的先天淋巴细胞（ILC）在不同的微环境中的信号不完全理解。在这里，我们表明，IL-7受体（IL-7 R）是不是严格需要的任何ILC子集的发展，残留的细胞持续存在于小肠固有层（siLP）的成年和新生儿Il 7 ra −/−小鼠。Il 7 ra −/− ILC 2主要表达ST 2 −表型，但不是炎性ILC 2。CCR 6 + ILC 3比其他ILC 3表达更高的Bcl-2，是Il 7 ra −/− siLP中最丰富的子集。所有ILC亚群在体外都具有功能活性，并且足以提供增强的对C感染的保护。啮齿动物。IL-15在体外同样维持野生型和Il 7 ra −/− ILC的存活，并补偿IL-7 R缺乏，因为在缺乏这两种分子的小鼠中，残留的ILC被耗尽。总的来说，这些数据表明siLP ILC不是完全IL-7 R依赖性的，但可以通过IL-15信号传导部分持续存在。ILC 2和ILC 3通常被认为需要IL-7。在此，作者使用IL-7 ko小鼠并提供了来自不同组织的ILC的并排比较，以表明IL-7信号传导对于肠道ILC的维持或功能不是必需的，并且IL-15可以补偿IL-7的缺乏。
The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra−/− mice. Il7ra−/− ILC2 primarily express an ST2− phenotype, but are not inflammatory ILC2. CCR6+ ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra−/− siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra−/− ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling. ILC2 and ILC3 are generally thought to require IL-7. Here the authors use IL-7 ko mice and provide side-by-side comparison of ILCs from different tissues to show that IL-7 signalling is not required for intestinal ILC maintenance or function and that IL-15 can compensate for absence of IL-7.