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
Affiliations
Luni Hu
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
Mengwei Han
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
Yichen Deng
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
Jingjing Gong
Institute of Systems Biomedicine, Peking University Health Science Center, Beijing 100191, China
Zhiyuan Hou
Institute of Systems Biomedicine, Peking University Health Science Center, Beijing 100191, China
Yanyu Zeng
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
Yime Zhang
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
Jing He
Department of Rheumatology and Immunology, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Peking University People’s Hospital, Beijing, China
Chao Zhong
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; Corresponding author
Summary: 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.
