Innate lymphoid cells (ILCs) promote tissue homeostasis and immune defense but also contribute to inflammatory diseases. ILCs exhibit phenotypic and functional plasticity in response to environmental stimuli, yet the transcriptional regulatory networks (TRNs) that control ILC function are largely unknown. Here, we integrate gene expression and chromatin accessibility data to infer regulatory interactions between transcription factors (TFs) and genes within intestinal type 1, 2, and 3 ILC subsets. We predicted the "core" TFs driving ILC identities, organized TFs into cooperative modules controlling distinct gene programs, and validated roles for c-MAF and BCL6 as regulators affecting type 1 and type 3 ILC lineages. The ILC network revealed alternative-lineage-gene repression, a mechanism that may contribute to reported plasticity between ILC subsets. By connecting TFs to genes, the TRNs suggest means to selectively regulate ILC effector functions, while our network approach is broadly applicable to identifying regulators in other in vivo cell populations.

中文翻译：

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促进和限制肠道先天淋巴细胞特性和功能的转录调控网络的特征。

先天性淋巴样细胞 (ILC) 促进组织稳态和免疫防御，但也会导致炎症性疾病。ILC 表现出响应环境刺激的表型和功能可塑性，但控制 ILC 功能的转录调控网络 (TRN) 在很大程度上是未知的。在这里，我们整合了基因表达和染色质可及性数据，以推断转录因子 (TF) 与肠道 1、2 和 3 型 ILC 子集中基因之间的调控相互作用。我们预测了驱动 ILC 身份的“核心”TF，将 TF 组织成控制不同基因程序的合作模块，并验证了 c-MAF 和 BCL6 作为影响 1 型和 3 型 ILC 谱系的调节因子的作用。ILC 网络揭示了替代谱系基因抑制，一种可能有助于报告 ILC 子集之间的可塑性的机制。通过将 TF 连接到基因，TRN 提出了选择性调节 ILC 效应子功能的方法，而我们的网络方法广泛适用于识别其他体内细胞群中的调节因子。