A cell type-specific transcriptomic approach to map B cell and monocyte type I interferon-linked pathogenic signatures in Multiple Sclerosis.
Adult
Apoptosis
B-Lymphocytes
/ immunology
Biomarkers
Case-Control Studies
Disease Susceptibility
Female
Gene Expression Profiling
Humans
Immunophenotyping
Interferon Type I
/ genetics
Interleukin-16
/ genetics
Male
Middle Aged
Monocytes
/ immunology
Multiple Sclerosis
/ etiology
Organ Specificity
/ genetics
Promoter Regions, Genetic
Signal Transduction
Transcriptome
Antiviral state
Apoptosis
B cell
Interferome
Monocyte
Relapsing-remitting multiple sclerosis
Transcriptome
Type I interferon signaling
Journal
Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
19
02
2019
revised:
08
04
2019
accepted:
08
04
2019
pubmed:
3
5
2019
medline:
21
7
2020
entrez:
4
5
2019
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 31047767
pii: S0896-8411(19)30094-0
doi: 10.1016/j.jaut.2019.04.006
pii:
doi:
Substances chimiques
Biomarkers
0
Interferon Type I
0
Interleukin-16
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-16Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.