Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Immunol. 2017 May;18(5):499-508. doi: 10.1038/ni.3712. Epub 2017 Mar 20.
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.
先天淋巴细胞 (ILCs) 与其他造血细胞和非造血细胞相互交流，以调节免疫、炎症和组织稳态。ILC 谱系如何发育和维持在很大程度上尚不清楚。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 组先天淋巴细胞 (ILC3) 中高水平表达。造血系统中 lncKdm2b 的缺失导致 ILC3 的数量和效应功能减少。lncKdm2b 通过激活转录因子 Zfp292 促进其增殖来维持 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) 复合物募集到 Zfp292 启动子上，从而启动其转录。Zfp292 或 Bptf 的缺失也消除了 ILC3 的维持，导致易受细菌感染。因此，我们的发现表明 lncRNAs 可能代表 ILC 发育和功能调节的另一个层面。
