Crinier Adeline, Kerdiles Yann, Vienne Margaux, Cózar Beatriz, Vivier Eric, Berruyer Carole
Aix Marseille University, CNRS, INSERM, CIML, Marseille, France.
Innate Pharma Research Laboratories, Innate Pharma, Marseille, France.
Semin Immunol. 2021 Feb;52:101424. doi: 10.1016/j.smim.2020.101424. Epub 2020 Dec 1.
Innate Lymphoid Cells (ILCs) are a recently described heterogeneous population of non-T, non-B lymphocytes. They are highly abundant at mucosal interfaces and, unlike T and B cells, they do not express somatically rearranged antigen-specific receptors. ILCs may be seen as the innate counterparts of T cells, but, major ILC deficiencies in humans appear to be clinically silent in modern conditions of hygiene and medicine, provided that T and B functions are preserved. NK cells are the founder members of this family and were originally classified in group 1 ILCs with ILC1s, due to similarities in cytokine production and development between these two types of cell. The classification of the ILC subsets was subsequently reviewed and five groups were defined on the basis of cytokine production and the discovery of specific transcription factors determining the different lineages. ILCs include NK cells, lymphoid tissue-inducer (LTi) cells and three other main subsets: ILC1s, ILC2s and ILC3s. The nature of distinct ILC1 population in mice and human is not consensual due to the high degree of similarity between ILCs and NK cells and their plastic relationships in some context. In this review, we will discuss the characteristics currently used for the phenotyping of NK cells and ILC1s in mice and humans, in the context of cancers especially, in which inappropriate discrimination between these two cell types can lead to erroneous conclusions regarding the specific impact of their targeting on tumors. Here, we suggest that multidimensional molecular controls, with the co-ordination of ontogeny-related signals, tissue-specific and tumor microenvironment-derived signals, determine the identity of NK cells and ILC1s. All these molecular stratifications contribute to the construction of cell fate for NK cells and ILC1s and account for the difficulties distinguishing between these two groups of cells.
固有淋巴细胞（ILCs）是最近描述的一类非T、非B淋巴细胞的异质性群体。它们在黏膜界面高度富集，与T细胞和B细胞不同，它们不表达体细胞重排的抗原特异性受体。ILCs可被视为T细胞的固有对应物，但是，在现代卫生和医学条件下，只要T细胞和B细胞的功能得以保留，人类主要的ILC缺陷在临床上似乎并无明显症状。自然杀伤细胞（NK细胞）是这个家族的创始成员，由于这两种细胞在细胞因子产生和发育方面存在相似性，最初与1型固有淋巴细胞（ILC1s）一起被归类为1组ILCs。随后对ILC亚群的分类进行了重新审视，并根据细胞因子的产生以及决定不同谱系的特异性转录因子的发现定义了五个组。ILCs包括NK细胞、淋巴组织诱导细胞（LTi细胞）以及其他三个主要亚群：ILC1s、ILC2s和ILC3s。由于ILCs与NK细胞之间的高度相似性以及它们在某些情况下的可塑性关系，小鼠和人类中不同的ILC1群体的性质尚无定论。在本综述中，我们将讨论目前用于小鼠和人类NK细胞和ILC1s表型分析的特征，特别是在癌症背景下，在这种情况下，对这两种细胞类型的不当区分可能导致关于它们靶向肿瘤的具体影响的错误结论。在此，我们认为多维度分子控制，与个体发育相关信号、组织特异性信号和肿瘤微环境衍生信号的协调，决定了NK细胞和ILC1s的身份。所有这些分子分层都有助于构建NK细胞和ILC1s的细胞命运，并解释了区分这两组细胞的困难。
