Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression
Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression
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通过启动 Zfp292 表达来维持 ILC3 需要长非编码 RNA lncKdm2b
DOI：
10.1038/ni.3712
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发表时间：
2017-05-01
影响因子：
30.5
通讯作者：
Fan, Zusen
中科院分区：
文献类型：
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作者：
Liu, Benyu;Ye, Buqing;Fan, Zusen
先天淋巴细胞 (ILC) 与其他造血和非造血细胞通讯，调节免疫、炎症和组织稳态。 ILC 谱系如何发展和维持仍然很大程度上未知。在这项研究中，我们观察到一种不同的长非编码 RNA (lncRNA) lncKdm2b 在肠道 3 组 ILC (ILC3s) 中高水平表达。造血系统中的 LncKdm2b 缺陷导致 ILC3 的数量和效应器功能减少。 LncKdm2b 表达通过激活转录因子 Zfp292 促进 ILC3 增殖，从而维持 ILC3 的维持。从机制上讲，lncKdm2b 将染色质组织者 Satb1 和核重塑因子 (NURF) 复合物招募到 Zfp292 启动子上以启动其转录。 Zfp292 或 Bptf 的缺失也会破坏 ILC3 的维持，导致对细菌感染的易感性。因此，我们的研究结果表明，lncRNA 可能代表了 ILC 发育和功能的另一层调节。
Innate lymphoid cells (ILCs) communicate with other hematopoietic and nonhematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How ILC lineages develop and are maintained remains largely unknown. In this study we observed that a divergent long noncoding RNA (lncRNA), lncKdm2b, was expressed at high levels in intestinal group 3 ILCs (ILC3s). LncKdm2b deficiency in the hematopoietic system led to reductions in the number and effector functions of ILC3s. LncKdm2b expression sustained the maintenance of ILC3s by promoting their proliferation through activation of the transcription factor Zfp292. Mechanistically, lncKdm2b recruited the chromatin organizer Satb1 and the nuclear remodeling factor (NURF) complex onto the Zfp292 promoter to initiate its transcription. Deletion of Zfp292 or Bptf also abrogated the maintenance of ILC3s, leading to susceptibility to bacterial infection. Therefore, our findings reveal that lncRNAs may represent an additional layer of regulation of ILC development and function.