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

Mohebiany, Alma Nazlie; Ramphal, Nishada Shakunty; Karram, Khalad; Di Liberto, Giovanni; Novkovic, Tanja; Klein, Matthias; Marini, Federico; Kreutzfeldt, Mario; Härtner, Franziska; Lacher, Sonja Maria; Bopp, Tobias; Mittmann, Thomas; Merkler, Doron; Waisman, Ari

doi:10.1016/j.celrep.2019.12.097

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Title		Microglial A20 protects the brain from CD8 T-cell-mediated immunopathology
Authors		Mohebiany, Alma Nazlie Ramphal, Nishada Shakunty Karram, Khalad Di Liberto, Giovanni Novkovic, Tanja Klein, Matthias Marini, Federico Kreutzfeldt, Mario Härtner, Franziska Lacher, Sonja Maria Bopp, Tobias Mittmann, Thomas Merkler, Doron Waisman, Ari 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		A20 — CD8 T cells — NF-κB — Microglia — Neuroinflammation
Identifiers		DOI: 10.1016/j.celrep.2019.12.097 PMID: 32023471
Full text		Article (Published version) (6.1 MB) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
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