An Unbiased Linkage Approach Reveals That the p53 Pathway Is Coupled to NK Cell Maturation.

Autor: Collin R; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., St-Pierre C; Institut de Recherche en Immunologie et en Cancérologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.; Département de Médecine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., Guilbault L; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., Mullins-Dansereau V; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., Policheni A; Molecular Genetics of Cancer Division, Immunology Division, Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia; and.; Department of Medical Biology, Melbourne University, Parkville, Victoria 3052, Australia., Guimont-Desrochers F; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., Pelletier AN; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., Gray DH; Molecular Genetics of Cancer Division, Immunology Division, Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia; and.; Department of Medical Biology, Melbourne University, Parkville, Victoria 3052, Australia., Drobetsky E; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada., Perreault C; Institut de Recherche en Immunologie et en Cancérologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.; Département de Médecine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada., Hillhouse EE; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; erinhillhouse@gmail.com Sylvie.lesage@umontreal.ca., Lesage S; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; erinhillhouse@gmail.com Sylvie.lesage@umontreal.ca.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
Jazyk: angličtina
Zdroj: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Aug 15; Vol. 199 (4), pp. 1490-1504. Date of Electronic Publication: 2017 Jul 14.
DOI: 10.4049/jimmunol.1600789
Abstrakt: Natural killer cells constitute potent innate lymphoid cells that play a major role in both tumor immunosurveillance and viral clearance via their effector functions. A four-stage model of NK cell functional maturation has been established according to the expression of CD11b and CD27, separating mature NK (mNK) cells into distinct populations that exhibit specific phenotypic and functional properties. To identify genetic factors involved in the regulation of NK cell functional maturation, we performed a linkage analysis on F 2 (B6.Rag1 -/- × NOD.Rag1 -/- intercross) mice. We identified six loci on chromosomes 2, 4, 7, 10, 11, and 18 that were linked to one or more mNK cell subsets. Subsequently, we performed an in silico analysis exploiting mNK cell subset microarray data, highlighting various genes and microRNAs as potential regulators of the functional maturation of NK cells. Together, the combination of our unbiased genetic linkage study and the in silico analysis positions genes known to affect NK cell biology along the specific stages of NK cell functional maturation. Moreover, this approach allowed us to uncover a novel candidate gene in the regulation of NK cell maturation, namely Trp53 Using mice deficient for Trp53 , we confirm that this tumor suppressor regulates NK cell functional maturation. Additional candidate genes revealed in this study may eventually serve as targets for the modulation of NK cell functional maturation to potentiate both tumor immunosurveillance and viral clearance.
(Copyright © 2017 by The American Association of Immunologists, Inc.)
Databáze: MEDLINE
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