title: NK Cell Proportion and Number Are Influenced by Genetic Loci on Chromosomes 8, 9, and 17.
abstract: NK cells play a crucial role in innate immunity due to their direct cytotoxicity toward tumors, virally infected cells, and stressed cells, and they also contribute to the orchestration of the adaptive response by their ability to produce immunoregulatory cytokines. In secondary lymphoid organs, NK cells compose the third most abundant lymphocyte subset after T cells and B cells. In this study, we perform an unbiased linkage analysis to determine the genetic loci that may limit the size of the NK cell compartment. Specifically, we exploit differences in NK cell proportion and absolute number between the C57BL/6 and the NOD mice. In addition to the previously identified linkage to chromosome 8, we find that a locus on chromosome 17, which encompasses the MHC locus, impacts NK cell number. Moreover, we identify a locus on mouse chromosome 9 that is strongly linked to the proportion and absolute number of NK cells. Using NOD congenic mice, we validate that both the MHC and the chromosome 9 loci influence the proportion and absolute number of NK cells. We have thus identified additional loci specifically linked to the proportion of NK cells and present some of the potential candidate genes comprised within these loci.
authors: Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
authors: Adam-Nicolas
authors: AN
authors: Pelletier
authors: Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
authors: Lorie
authors: http://orcid.org/0000-0003-1313-2179
authors: L
authors: Guilbault
authors: Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
authors: Fanny
authors: http://orcid.org/0000-0001-8371-1921
authors: F
authors: Guimont-Desrochers
authors: Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and.
authors: Erin E
authors: EE
authors: Hillhouse
authors: Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada sylvie.lesage@umontreal.ca.
authors: Sylvie
authors: http://orcid.org/0000-0002-0968-2795
authors: S
authors: Lesage
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000276:immunology*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000276:immunology*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D008040:Genetic Linkage; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000276:immunology; D016688:Mice, Inbred NOD / Q000235:genetics / Q000276:immunology; D008822:Mice, Transgenic