气候变化领域集成服务门户(CCPortal): Host genetic control of natural killer cell diversity revealed in the Collaborative Cross

CCPortal

DOI	10.1073/pnas.2018834118
	Host genetic control of natural killer cell diversity revealed in the Collaborative Cross
	Dupont M.S.J.; Guillemot V.; Campagne P.; Serafini N.; Marie S.; Montagutelli X.; Di Santo J.P.; Vosshenrich C.A.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Natural killer (NK) cells are innate effectors armed with cytotoxic and cytokine-secreting capacities whose spontaneous antitumor activity is key to numerous immunotherapeutic strategies. However, current mouse models fail to mirror the extensive immune system variation that exists in the human population which may impact on NK cell-based therapies. We performed a comprehensive profiling of NK cells in the Collaborative Cross (CC), a collection of novel recombinant inbred mouse strains whose genetic diversity matches that of humans, thereby providing a unique and highly diverse small animal model for the study of immune variation. We demonstrate that NK cells from CC strains displayed a breadth of phenotypic and functional variation reminiscent of that reported for humans with regards to cell numbers, key marker expression, and functional capacities. We took advantage of the vast genetic diversity of the CC and identified nine genomic loci through quantitative trait locus mapping driving these phenotypic variations. SNP haplotype patterns and variant effect analyses identified candidate genes associated with lung NK cell numbers, frequencies of CD94+ NK cells, and expression levels of NKp46. Thus, we demonstrate that the CC represents an outstanding resource to study NK cell diversity and its regulation by host genetics. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Collaborative cross; Innate immunity; NK cells; Quantitative trait locus mapping
语种	英语
scopus关键词	natural cytotoxicity triggering receptor 1; adult; animal cell; animal experiment; animal tissue; Article; cell count; Collaborative Cross mouse; controlled study; female; gene identification; gene locus; genetic association; genetic regulation; genetic variability; haplotype; innate immunity; lymphocyte differentiation; mouse; natural killer cell; nonhuman; phenotypic variation; priority journal; protein expression; protein expression level; quantitative trait locus mapping; single nucleotide polymorphism
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180389
作者单位	Innate Immunity Unit, Immunology Department, Institut Pasteur, Paris, 75724, France; INSERM U1223, Paris, 75724, France; Université de Paris, Sorbonne Paris Cité, Paris, 75013, France; Bioinformatics and Biostatistics Hub, Computational Biology Department, Institut Pasteur, Paris, 75724, France; Mouse Genetics Laboratory, Department of Genomes and Genetics, Institut Pasteur, Paris, 75724, France
推荐引用方式 GB/T 7714	Dupont M.S.J.,Guillemot V.,Campagne P.,et al. Host genetic control of natural killer cell diversity revealed in the Collaborative Cross[J],2021,118(10).
APA	Dupont M.S.J..,Guillemot V..,Campagne P..,Serafini N..,Marie S..,...&Vosshenrich C.A.J..(2021).Host genetic control of natural killer cell diversity revealed in the Collaborative Cross.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Dupont M.S.J.,et al."Host genetic control of natural killer cell diversity revealed in the Collaborative Cross".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).