Genetic distinction between functional tissue-resident and conventional natural killer cells

• Published in: iScience Vol. 26; no. 7; p. 107187
• Main Authors: Hu, Luni, Han, Mengwei, Deng, Yichen, Gong, Jingjing, Hou, Zhiyuan, Zeng, Yanyu, Zhang, Yime, He, Jing, Zhong, Chao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.07.2023; Elsevier
• Subjects: Biological sciences; Epigenetics; Immunology; Molecular biology; Epigenetics; Biological sciences; Immunology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107187

Tissue-residential natural killer (trNK) cells act as pioneering responders during infectious challenges. However, their discrimination with conventional NK (cNK) cells is still an issue. Through an integrative transcriptome comparison of the two NK subgroups from different tissues, we have defined two genesets capable of efficiently distinguishing them. Based on the two genesets, a fundamental difference between the activation of trNK and cNK is identified and further confirmed. Mechanistically, we have discovered a particular role of chromatin landscape in regulating the trNK activation. In addition, IL-21R and IL-18R are respectively highly expressed by trNK and cNK, indicating a role of cytokine milieu in determining their differential activation. Indeed, IL-21 is particularly critical in accessorily promoting trNK activation using a bunch of bifunctional transcription factors. Together, this study sheds light on the bona fide difference between trNK and cNK, which will further expand our knowledge about their distinct functionalities during immune responses. [Display omitted] •Defining trNK and cNK genesets to efficiently distinguish the two NK populations•Revealing the essential role of chromatin landscape in determining trNK activation•Discovering the involvement of particular transcription factors in cNK activation•Identifying the different responsiveness of trNK and cNK to IL-21 and IL-18 Biological sciences; Molecular biology; Epigenetics; Immunology