RRC ID 46360
著者 Didonna A, Cekanaviciute E, Oksenberg JR, Baranzini SE.
タイトル Immune cell-specific transcriptional profiling highlights distinct molecular pathways controlled by Tob1 upon experimental autoimmune encephalomyelitis.
ジャーナル Sci Rep
Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by focal lymphocytic infiltration, demyelination and neurodegeneration. Despite the recent advances in understanding MS molecular basis, no reliable biomarkers have been identified yet to monitor disease progression. Our group has previously reported that low levels of TOB1 in CD4(+) T cells are strongly associated with a higher risk of MS conversion in individuals experiencing an initial demyelinating event. Consistently, Tob1 ablation in mice exacerbates the clinical phenotype of the MS model experimental autoimmune encephalomyelitis (EAE). To shed light on Tob1 molecular functions in the immune system, we have conducted the first cell-based transcriptomic analysis in Tob1(-/-) and wildtype mice upon EAE. Next-generation sequencing was employed to characterize the changes in gene expression in T and B cells at pre- and post-symptomatic EAE stages. Remarkably, we found only modest overlap among the different genetic signatures, suggesting that Tob1 may control distinct genetic programs in the different cytotypes. This hypothesis was corroborated by gene ontology and global interactome analyses, which highlighted specific cellular pathways in each cellular subset before and after EAE induction. In summary, our work pinpoints a multifaceted activity of Tob1 in both homeostasis and disease progression.
巻・号 6
ページ 31603
公開日 2016-8-22
DOI 10.1038/srep31603
PII srep31603
PMID 27546286
PMC PMC4992865
MeSH Animals B-Lymphocytes / immunology* B-Lymphocytes / pathology CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / pathology Carrier Proteins / genetics Carrier Proteins / immunology* Encephalomyelitis, Autoimmune, Experimental / genetics Encephalomyelitis, Autoimmune, Experimental / immunology* Encephalomyelitis, Autoimmune, Experimental / pathology Gene Expression Profiling* Intracellular Signaling Peptides and Proteins Mice Mice, Knockout Multiple Sclerosis / genetics Multiple Sclerosis / immunology* Multiple Sclerosis / pathology NIH 3T3 Cells Signal Transduction / genetics Signal Transduction / immunology*
IF 3.998
引用数 5
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
実験動物マウス RBRC01765