Natural killer (NK) cells are cytotoxic innate lymphocytes that are well-known for their ability to kill infected or malignant cells. Beyond their roles in tumor surveillance and anti-pathogen defense, more recent studies have highlighted key roles for NK cells in a broad range of biological processes, including metabolic homeostasis, immunomodulation of T cells, contact hypersensitivity, and pregnancy. Consistent with the breadth and diversity of these functions, it is now appreciated that NK cells are a heterogeneous population, comprised of specialized and sometimes tissue-specific subsets with distinct phenotypes and effector functions. Indeed, in addition to the conventional NK cells (cNKs) that are abundant and have been well-studied in the blood and spleen, distinct subsets of tissue-resident NK cells (trNKs) and “helper” Group 1 innate lymphoid cells (ILC1s) have now been described in multiple organs and tissues, including the liver, uterus, thymus, adipose tissue, and skin, among others. The cNK, trNK, and/or helper ILC1 populations that co-exist in these various tissues exhibit both common and distinct developmental requirements, suggesting that a combination of lineage–, subset–, and tissue–specific differentiation processes may contribute to the unique functional properties of these various populations. Here, we provide an overview of the transcriptional regulatory pathways known to instruct the development and differentiation of cNK, trNK, and helper ILC1 populations in specific tissues in mice.

自然杀伤 (NK) 细胞是细胞毒性的先天淋巴细胞，以其杀死受感染或恶性细胞的能力而闻名。除了在肿瘤监测和抗病原体防御中的作用之外，最近的研究还强调了 NK 细胞在广泛的生物过程中的关键作用，包括代谢稳态、T 细胞的免疫调节、接触性超敏反应和妊娠。与这些功能的广度和多样性相一致，现在人们认识到 NK 细胞是一个异质群体，由具有不同表型和效应功能的专门的、有时是组织特异性的亚群组成。事实上，除了血液和脾脏中丰富且已得到充分研究的传统 NK 细胞 (cNK) 之外，组织驻留 NK 细胞 (trNK) 和“辅助”第 1 组先天淋巴细胞 (ILC1) 的不同亚群现已在多个器官和组织中得到描述，包括肝脏、子宫、胸腺、脂肪组织和皮肤等。共存于这些不同组织中的 cNK、trNK 和/或辅助 ILC1 群体表现出共同和独特的发育要求，表明谱系、子集和组织特异性分化过程的组合可能有助于独特的功能这些不同群体的特性。在这里，我们概述了已知指导小鼠特定组织中 cNK、trNK 和辅助 ILC1 群体发育和分化的转录调控途径。