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New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis

Item Type:Article
Title:New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis
Creators Name:Hoppmann, N. and Graetz, C. and Paterka, M. and Poisa-Beiro, L. and Larochelle, C. and Hasan, M. and Lill, C.M. and Zipp, F. and Siffrin, V.
Abstract:Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system, which is thought to be triggered by environmental factors in genetically susceptible individuals leading to activation of autoreactive T lymphocytes. Large multi-centre genome-wide association studies have identified multiple genetic risk loci in multiple sclerosis. In this study, we investigated T cell transcriptomic changes in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We correlated these findings with the multiple sclerosis risk genes postulated by the most recent Immunochip analysis and found that multiple sclerosis susceptibility genes were significantly regulated in experimental autoimmune encephalomyelitis. Our data indicate that nine distinct genes associated with multiple sclerosis risk, Bach2, Il2ra, Irf8, Mertk, Odf3b, Plek, Rgs1, Slc30a7 and Thada, can be confirmed to be differentially regulated in pathogenic CD4(+) T cells. During the effector phase within the inflamed CNS, CD4(+) T cells undergo comprehensive transformation and we identified key transcription factors and signalling networks involved in this process. The transformation was linked to metabolic changes with the involvement of liver X receptor/retinoid X receptor signalling and cholesterol biosynthesis, which might control the T cell effector function in the central nervous system. Thus, our study confirms the involvement of multiple sclerosis risk genes in the pathophysiology of the animal model and sheds light on additional disease-relevant inflammatory networks.
Keywords:Multiple Sclerosis, Experimental Autoimmune Encephalomyelitis, Transcriptome Analysis, Plasticity, GWAS, Animals, Mice
Source:Brain
ISSN:0006-8950
Publisher:Oxford University Press (U.K.)
Volume:138
Number:Pt 4
Page Range:902-917
Date:April 2015
Official Publication:https://doi.org/10.1093/brain/awu408
PubMed:View item in PubMed

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