Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity

Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases, such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses...

Full description

Bibliographic Details
Main Authors:	Bearoff, Frank, del Rio, Roxana, Case, Laure K., Dragon, Julie A., Nguyen-Vu, Trang, Lin, Chin-Yo, Blankenhorn, Elizabeth P., Teuscher, Cory, Krementsov, Dimitry N.
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133152/

id	pubmed-5133152
recordtype	oai_dc
spelling	pubmed-51331522017-03-22 Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity Bearoff, Frank del Rio, Roxana Case, Laure K. Dragon, Julie A. Nguyen-Vu, Trang Lin, Chin-Yo Blankenhorn, Elizabeth P. Teuscher, Cory Krementsov, Dimitry N. Article Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases, such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naïve immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific, and sex-specific. Bioinformatic analysis of the genetically-controlled transcript networks reveals reduced cell type-specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared to PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease. 2016-09-22 2016-12 /pmc/articles/PMC5133152/ /pubmed/27653816 http://dx.doi.org/10.1038/gene.2016.37 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bearoff, Frank del Rio, Roxana Case, Laure K. Dragon, Julie A. Nguyen-Vu, Trang Lin, Chin-Yo Blankenhorn, Elizabeth P. Teuscher, Cory Krementsov, Dimitry N.
spellingShingle	Bearoff, Frank del Rio, Roxana Case, Laure K. Dragon, Julie A. Nguyen-Vu, Trang Lin, Chin-Yo Blankenhorn, Elizabeth P. Teuscher, Cory Krementsov, Dimitry N. Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
author_facet	Bearoff, Frank del Rio, Roxana Case, Laure K. Dragon, Julie A. Nguyen-Vu, Trang Lin, Chin-Yo Blankenhorn, Elizabeth P. Teuscher, Cory Krementsov, Dimitry N.
author_sort	Bearoff, Frank
title	Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
title_short	Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
title_full	Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
title_fullStr	Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
title_full_unstemmed	Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
title_sort	natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to cns autoimmunity
description	Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases, such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naïve immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific, and sex-specific. Bioinformatic analysis of the genetically-controlled transcript networks reveals reduced cell type-specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared to PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133152/
_version_	1613752094230052864

Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity

Similar Items