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

Luni Hu; Mengwei Han; Yichen Deng; Jingjing Gong; Zhiyuan Hou; Yanyu Zeng; Yime Zhang; Jing He; Chao Zhong

doi:10.1016/j.isci.2023.107187

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

iScience. 2023 Jun 20;26(7):107187. doi: 10.1016/j.isci.2023.107187. eCollection 2023 Jul 21.

Authors

Luni Hu¹, Mengwei Han¹, Yichen Deng¹, Jingjing Gong², Zhiyuan Hou², Yanyu Zeng¹, Yime Zhang¹, Jing He³, Chao Zhong¹

Affiliations

¹ Institute of Systems Biomedicine, Department of Immunology, NHC Key Laboratory of Medical Immunology (Peking University), Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
² Institute of Systems Biomedicine, Peking University Health Science Center, Beijing 100191, China.
³ Department of Rheumatology and Immunology, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Peking University People's Hospital, Beijing, China.

Abstract

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.

Keywords: Biological sciences; Epigenetics; Immunology; Molecular biology.