An unbiased linkage approach reveals that the p53 pathway Is coupled to NK cell maturation

Collin, R; St-Pierre, C; Guilbault, L; Mullins-Dansereau, V; Policheni, A; Guimont-Desrochers, F; Pelletier, AN; Gray, DH; Drobetsky, E; Perreault, C; Hillhouse, EE; Lesage, S

Author(s): Collin, R; St-Pierre, C; Guilbault, L; Mullins-Dansereau, V; Policheni, A; Guimont-Desrochers, F; Pelletier, AN; Gray, DH; Drobetsky, E; Perreault, C; Hillhouse, EE; Lesage, S;
Details: Publication Year 2017-08-15,Volume 199,Issue #4,Page 1490-1504
Journal Title: Journal of Immunology
Publication Type: Journal Article
Abstract: 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 F2 (B6.Rag1-/- x 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.
Publisher: Am Assoc Immunologists
Research Division(s): Molecular Genetics Of Cancer
PubMed ID: 28710252
Publisher's Version: https://doi.org/10.4049/jimmunol.1600789
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-08-30 02:22:42

Last Modified: 2017-09-05 08:48:47