Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription.,Journal of Experimental Medicine

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Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-08-21 , DOI: 10.1084/jem.20182363
Benyu Liu ₁ , Liuliu Yang _{1,

2} , Xiaoxiao Zhu ₃ , Huimu Li _{1,

2} , Pingping Zhu ₁ , Jiayi Wu _{1,

2} , Tiankun Lu _{1,

2} , Luyun He _{1,

2} , Nian Liu _{1,

2} , Shu Meng ₃ , Liang Zhou ₄ , Buqing Ye ₅ , Yong Tian _{2,

6} , Zusen Fan _{2,

5}

Affiliation

Innate lymphoid cells (ILCs) play critical roles in defending infections and maintaining mucosal homeostasis. All ILCs arise from common lymphoid progenitors (CLPs) in bone marrow. However, how CLPs stratify and differentiate into ILC lineages remains elusive. Here, we showed that Yeats4 is highly expressed in ILCs and their progenitors. Yeats4 conditional KO in the hematopoietic system causes decreased numbers of ILCs and impairs their effector functions. Moreover, Yeats4 regulates α4β7 + CLP differentiation toward common helper ILC progenitors (CHILPs). Mechanistically, Yeats4 recruits the Dot1l-RNA Pol II complex onto Lmo4 promoter through recognizing H3K27ac modification to initiate Lmo4 transcription in α4β7 + CLPs. Additionally, Lmo4 deficiency also impairs ILC lineage differentiation and their effector functions. Collectively, the Yeats4-Lmo4 axis is required for ILC lineage commitment.

中文翻译：

Yeats4通过激活Lmo4转录来驱动ILC谱系承诺。

先天性淋巴样细胞（ILC）在防御感染和维持粘膜稳态方面起着至关重要的作用。所有ILC均来自骨髓中常见的淋巴样祖细胞（CLP）。但是，CLP如何分层并分化为ILC谱系仍然难以捉摸。在这里，我们表明Yeats4在ILC及其祖细胞中高度表达。造血系统中的Yeats4条件性KO导致ILC数量减少并损害其效应子功能。此外，Yeats4调节α4β7+ CLP向普通辅助ILC祖细胞（CHILP）的分化。从机制上讲，Yeats4通过识别H3K27ac修饰以启动α4β7+ CLP中的Lmo4转录，将Dotl1-RNA Pol II复合物募集到Lmo4启动子上。此外，Lmo4缺乏症也会损害ILC谱系分化及其效应子功能。总的来说，

更新日期：2019-11-04

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