Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription
Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription
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Yeats4 通过激活 Lmo4 转录来驱动 ILC 谱系定型
DOI：
10.1084/jem.20182363
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发表时间：
2019-11-01
影响因子：
15.3
通讯作者：
Fan, Zusen
中科院分区：
文献类型：
--
作者：
Liu, Benyu;Yang, Liuliu;Fan, Zusen
先天淋巴细胞（ILC）在防御感染和维持粘膜稳态方面发挥着关键作用。所有 ILC 均源自骨髓中的共同淋巴祖细胞 (CLP)。然而，CLP 如何分层并分化为 ILC 谱系仍不清楚。在这里，我们表明 Yeats4 在 ILC 及其祖细胞中高度表达。 Yeats4 造血系统中的条件性敲除会导致 ILC 数量减少并损害其效应功能。此外，Yeats4 调节 alpha(4)beta(+)(7) CLP 向常见辅助 ILC 祖细胞 (CHILP) 的分化。从机制上讲，Yeats4 通过识别 H3K27ac 修饰将 Dot1l-RNA Pol II 复合物募集到 Lmo4 启动子上，从而启动 alpha(4)beta(+)(7) CLP 中的 Lmo4 转录。此外，Lmo4 缺乏还会损害 ILC 谱系分化及其效应子功能。总的来说，Yeats4-Lmo4 轴是 ILC 谱系承诺所必需的。
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 alpha(4)beta(+)(7) 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 alpha(4)beta(+)(7) CLPs. Additionally, Lmo4 deficiency also impairs ILC lineage differentiation and their effector functions. Collectively, the Yeats4-Lmo4 axis is required for ILC lineage commitment.