Journal
CELL REPORTS
Volume 30, Issue 5, Pages 1585-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.12.097
Keywords
-
Categories
Funding
- IMB Microscopy Core Facility
- Deutsch Forschungsgemeinschaft (DFG) [CRC/TR 128, AW1600/10-1, CRC1080 TPC02, CRC TR128]
- EU ITN grant NeuroKine
- National Multiple Sclerosis Society (NMSS) [RG 1707-28780]
- Swiss National Science Foundation
- Swiss MS Society
- Helmut Horten Foundation
- ESR fellowship under the Marie Curie Action ITN project NeuroKine
Ask authors/readers for more resources
Tumor-necrosis-factor-alpha-induced protein 3 (TNFAIP3), or A20, is a ubiquitin-modifying protein and negative regulator of canonical nuclear factor kappa B (NF-kappa B) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available