UNIGE document Scientific Article
previous document  unige:131892  next document
add to browser collection
Title

Microglial A20 protects the brain from CD8 T-cell-mediated immunopathology

Authors
Mohebiany, Alma Nazlie
Ramphal, Nishada Shakunty
Karram, Khalad
Novkovic, Tanja
Klein, Matthias
Marini, Federico
show hidden authors show all authors [1 - 14]
Published in Cell Reports. 2020, vol. 30, no. 5, p. 1585-1597.e6
Abstract Tumor-necrosis-factor-alpha-induced protein 3 (TNFAIP3), or A20, is a ubiquitin-modifying protein and negative regulator of canonical nuclear factor κB (NF-κB) signaling. Several single-nucleotide polymorphisms in TNFAIP3 are associated with autoimmune diseases, suggesting a role in tissue inflammation. While the role of A20 in peripheral immune cells has been well investigated, less is known about its role in the central nervous system (CNS). Here, we show that microglial A20 is crucial for maintaining brain homeostasis. Without microglial A20, CD8+ T cells spontaneously infiltrate the CNS and acquire a viral response signature. The combination of infiltrating CD8+ T cells and activated A20-deficient microglia leads to an increase in VGLUT1+ terminals and frequency of spontaneous excitatory currents. Ultimately, A20-deficient microglia upregulate genes associated with the antiviral response and neurodegenerative diseases. Together, our data suggest that microglial A20 acts as a sensor for viral infection and a master regulator of CNS homeostasis.
Keywords A20CD8 T cellsNF-κBMicrogliaNeuroinflammation
Identifiers
PMID: 32023471
Full text
Article (Published version) (6.1 MB) - public document Free access
Structures
Research group La Sclérose en plaques (908)
Citation
(ISO format)
MOHEBIANY, Alma Nazlie et al. Microglial A20 protects the brain from CD8 T-cell-mediated immunopathology. In: Cell Reports, 2020, vol. 30, n° 5, p. 1585-1597.e6. doi: 10.1016/j.celrep.2019.12.097 https://archive-ouverte.unige.ch/unige:131892

198 hits

114 downloads

Update

Deposited on : 2020-03-09

Export document
Format :
Citation style :