title: Immune cell-specific transcriptional profiling highlights distinct molecular pathways controlled by Tob1 upon experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California 94158, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Didonna
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California 94158, USA.
authors.forename: Egle
authors.initials: E
authors.lastname: Cekanaviciute
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California 94158, USA.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California 94158, USA.
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D041681:NIH 3T3 Cells; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490903:Tob1 protein, mouse