A cell type-specific transcriptomic approach to map B cell and monocyte type I interferon-linked pathogenic signatures in Multiple Sclerosis: Journal of Autoimmunity

M Severa, F Rizzo, S Srinivasan, M Di Dario, E Giacomini, MC Buscarinu, M Cruciani, MP Etna, S Sandini, R Mechelli, A Farina, P Trivedi, PJ Hertzog, M Salvetti, C Farina, EM Coccia

Research output: Contribution to journalArticlepeer-review

Abstract

Alteration in endogenous Interferon (IFN) system may profoundly impact immune cell function in autoimmune diseases. Here, we provide evidence that dysregulation in IFN-regulated genes and pathways are involved in B cell- and monocyte-driven pathogenic contribution to Multiple Sclerosis (MS) development and maintenance. In particular, by using an Interferome-based cell type-specific approach, we characterized an increased susceptibility to an IFN-linked caspase-3 dependent apoptotic cell death in both B cells and monocytes of MS patients that may arise from their chronic activation and persistent stimulation by activated T cells. Ongoing caspase-3 activation functionally impacts on MS monocyte properties influencing the STAT-3/IL-16 axis, thus, driving increased expression and massive release of the bio-active IL-16 triggering and perpetuating CD4+ T cell migration. Importantly, our analysis also identified a previously unknown multi-component defect in type I IFN-mediated signaling and response to virus pathways specific of MS B cells, impacting on induction of anti-viral responses and Epstein-barr virus infection control in patients. Taking advantage of cell type-specific transcriptomics and in-depth functional validation, this study revealed pathogenic contribution of endogenous IFN signaling and IFN-regulated cell processes to MS pathogenesis with implications on fate and functions of B cells and monocytes that may hold therapeutic potential. © 2019 Elsevier Ltd
Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalJournal of Autoimmunity
Volume101
DOIs
Publication statusPublished - 2019

Fingerprint Dive into the research topics of 'A cell type-specific transcriptomic approach to map B cell and monocyte type I interferon-linked pathogenic signatures in Multiple Sclerosis: Journal of Autoimmunity'. Together they form a unique fingerprint.

Cite this