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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
Genes and immunity, v 17(7), pp 386-395
22 Sep 2016
PMCID: PMC5133152
PMID: 27653816
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity
- Creators
- Frank Bearoff - Drexel UniversityRoxana del Rio - University of VermontLaure K. Case - Jackson LaboratoryJulie A. Dragon - University of VermontTrang Nguyen-Vu - Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry University of Houston Houston TX USAChin-Yo Lin - Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry University of Houston Houston TX USAElizabeth P. Blankenhorn - Drexel UniversityCory Teuscher - University of VermontDimitry N. Krementsov - University of Vermont
- Publication Details
- Genes and immunity, v 17(7), pp 386-395
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000390424000003
- Scopus ID
- 2-s2.0-84988674609
- Other Identifier
- 991019168582204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity
- Immunology