A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation

Sofie Voet, Conor Mc Guire, Nora Hagemeyer, Arne Martens, Anna Schroeder, Peter Wieghofer, Carmen Daems, Ori Staszewski, Lieselotte Vande Walle, Marta Joana Costa Jordao, Mozes Sze, Hanna-Kaisa Vikkula, Delphine Demeestere, Griet Van Imschoot, Charlotte L. Scott, Esther Hoste, Amanda Goncalves, Martin Guilliams, Saskia Lippens, Claude LibertRoos E. Vandenbroucke, Ki-Wook Kim, Steffen Jung, Zsuzsanna Callaerts-Vegh, Patrick Callaerts, Joris de Wit, Mohamed Lamkanfi, Marco Prinz, Geert van Loo

Research output: Contribution to journalArticlepeer-review


Microglia, the mononuclear phagocytes of the central nervous system (CNS), are important for the maintenance of CNS homeostasis, but also critically contribute to CNS pathology. Here we demonstrate that the nuclear factor kappa B (NF-kappa B) regulatory protein A20 is crucial in regulating microglia activation during CNS homeostasis and pathology. In mice, deletion of A20 in microglia increases microglial cell number and affects microglial regulation of neuronal synaptic function. Administration of a sublethal dose of lipopolysaccharide induces massive microglia activation, neuroinflammation, and lethality in mice with microgliaconfined A20 deficiency. Microglia A20 deficiency also exacerbates multiple sclerosis (MS) like disease, due to hyperactivation of the NIrp3 inflammasome leading to enhanced interleukin-113 secretion and CNS inflammation. Finally, we confirm a NIrp3 inflammasome signature and IL-1 beta expression in brain and cerebrospinal fluid from MS patients. Collectively, these data reveal a critical role for A20 in the control of microglia activation and neuroinflammation.

Original languageEnglish
Article number2036
Number of pages15
JournalNature Communications
Issue number1
StatePublished - 23 May 2018

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation'. Together they form a unique fingerprint.

Cite this