PDF(Pubmed)
Abstract：
Group 2 innate lymphoid cells (ILC2s) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 is a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains unclear. Herein, we identify ILC2-specific GATA3-related tandem super-enhancers (G3SE) that induce high GATA3 in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 deficiency in the bone marrow, lung, liver, and small intestine with minimal impact on other ILC lineages or Th2 cells. Single-cell RNA-sequencing and subsequent flow cytometry analysis show that GATA3 induction mechanism, which is required for entering the ILC2 stage, is lost in IL-17RB+PD-1- late ILC2-committed precursor stage in G3SE-deficient mice. Cnot6l, part of the CCR4-NOT deadenylase complex, is a possible GATA3 target during ILC2 development. Our findings implicate a stage-specific regulatory mechanism for GATA3 expression during ILC2 development.
摘要：
第2组先天淋巴细胞（ILC2s）是产生2型细胞因子的先天淋巴细胞的一个子集，包括IL-4、IL-5和IL-13。GATA3是ILC2多阶段发育的关键转录因子。然而,GATA3何时以及如何诱导到ILC2发育所需的水平尚不清楚.在这里，我们鉴定了ILC2特异性GATA3相关的串联超级增强子（G3SE），其在ILC2定向前体中诱导高GATA3。G3SE缺陷小鼠在骨髓中表现出ILC2缺陷，肺，肝脏,和小肠，对其他ILC谱系或Th2细胞影响最小。单细胞RNA测序和随后的流式细胞术分析表明，GATA3诱导机制，这是进入ILC2阶段所必需的，在G3SE缺陷小鼠中IL-17RB+PD-1-晚期ILC2-定向前体阶段丢失。Cnot6l,CCR4-NOT死酶复合物的一部分，是ILC2开发过程中可能的GATA3目标。我们的发现暗示了ILC2发育过程中GATA3表达的阶段特异性调控机制。
