Advanced search
1 file | 4.65 MB

A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation

Author
Organization
Abstract
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.
Keywords
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, NF-KAPPA-B, NLRP3, INFLAMMASOME, ALZHEIMERS-DISEASE, MYELOID CELLS, CNS, MACROPHAGES, GENE, HOMEOSTASIS, ARTHRITIS

Downloads

  • 3050 18Voet.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 4.65 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Voet, Sofie, Conor Mc Guire, Nora Hagemeyer, Arne Martens, Anna Schroeder, Peter Wieghofer, Carmen Daems, et al. 2018. “A20 Critically Controls Microglia Activation and Inhibits Inflammasome-dependent Neuroinflammation.” Nature Communications 9.
APA
Voet, Sofie, Mc Guire, C., Hagemeyer, N., Martens, A., Schroeder, A., Wieghofer, P., Daems, C., et al. (2018). A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. NATURE COMMUNICATIONS, 9.
Vancouver
1.
Voet S, Mc Guire C, Hagemeyer N, Martens A, Schroeder A, Wieghofer P, et al. A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. NATURE COMMUNICATIONS. 2018;9.
MLA
Voet, Sofie, Conor Mc Guire, Nora Hagemeyer, et al. “A20 Critically Controls Microglia Activation and Inhibits Inflammasome-dependent Neuroinflammation.” NATURE COMMUNICATIONS 9 (2018): n. pag. Print.
@article{8565450,
  abstract     = {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.},
  articleno    = {2036},
  author       = {Voet, Sofie and Mc Guire, Conor and Hagemeyer, Nora and Martens, Arne and Schroeder, Anna and Wieghofer, Peter and Daems, Carmen and Staszewski, Ori and Vande Walle, Lieselotte and Jordao, Marta Joana Costa and Sze, Mozes and Vikkula, Hanna-Kaisa and Demeestere, Delphine and Van Imschoot, Griet and Scott, Charlotte and Hoste, Esther and Gon\c{c}alves, Amanda and Guilliams, Martin and Lippens, Saskia and Libert, Claude and Vandenbroucke, Roosmarijn and Kim, Ki-Wook and Jung, Steffen and Callaerts-Vegh, Zsuzsanna and Callaerts, Patrick and de Wit, Joris and Lamkanfi, Mohamed and Prinz, Marco and van Loo, Geert},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  language     = {eng},
  pages        = {15},
  title        = {A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation},
  url          = {http://dx.doi.org/10.1038/s41467-018-04376-5},
  volume       = {9},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: