Since their discovery a decade ago, it has become evident that innate lymphoid cells (ILCs) play critical roles in protective immune responses against intracellular and extracellular pathogens but are also central regulators of epithelial barrier integrity and tissue homeostasis. ILCs populate almost every tissue in mammalian organisms; therefore, not surprisingly, dysregulation of their functions contributes to the development and progression of multiple inflammatory and metabolic diseases. Our knowledge of the transcriptional programs governing the development, differentiation, and functions of the different groups of ILCs has increased dramatically in the last ten years. However, with the advent of new technologies, an unprecedented level of heterogeneity, plasticity, and developmental complexity has started to be revealed. In this review, we highlight recent advances in our understanding of ILC development and their biological functions. In particular, we aim to emphasize how our increasing knowledge of the chromatin landscape and the noncoding genome of these innate lymphocytes is allowing us to better understand their development and functions in different contexts during homeostasis and inflammation. Moreover, we propose that the design of more refined genetic tools to study tissue‐specific ILCs and their functions can be accomplished by leveraging our understanding of how specific noncoding elements of the genome regulate gene expression in ILCs.

中文翻译：

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先天淋巴细胞和非编码基因组的个体发育和异质性

自十年前发现以来，先天淋巴细胞 (ILC) 在针对细胞内和细胞外病原体的保护性免疫反应中发挥关键作用，但也是上皮屏障完整性和组织稳态的中心调节剂，这一点已经变得很明显。ILC 几乎存在于哺乳动物生物体的所有组织中；因此，毫不奇怪，它们的功能失调会导致多种炎症和代谢疾病的发生和发展。在过去十年中，我们对控制不同 ILC 组发育、分化和功能的转录程序的了解急剧增加。然而，随着新技术的出现，前所未有的异质性、可塑性和发展复杂性已经开始显现。在这次审查中，我们强调了我们对 ILC 发展及其生物学功能的理解的最新进展。特别是，我们旨在强调我们对染色质景观和这些先天淋巴细胞的非编码基因组的日益了解如何使我们能够更好地了解它们在稳态和炎症过程中在不同背景下的发育和功能。此外，我们建议通过利用我们对基因组特定非编码元件如何调节 ILC 中基因表达的理解，设计更精细的遗传工具来研究组织特异性 ILC 及其功能。我们的目标是强调我们对染色质景观和这些先天淋巴细胞的非编码基因组的日益了解如何使我们能够更好地了解它们在稳态和炎症过程中在不同背景下的发育和功能。此外，我们建议通过利用我们对基因组特定非编码元件如何调节 ILC 中基因表达的理解，设计更精细的遗传工具来研究组织特异性 ILC 及其功能。我们的目标是强调我们对染色质景观和这些先天淋巴细胞的非编码基因组的日益了解如何使我们能够更好地了解它们在稳态和炎症过程中在不同背景下的发育和功能。此外，我们建议通过利用我们对基因组特定非编码元件如何调节 ILC 中基因表达的理解，设计更精细的遗传工具来研究组织特异性 ILC 及其功能。