
A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation
- Author
- Sofie Voet, Conor Mc Guire (UGent) , Nora Hagemeyer, Arne Martens (UGent) , Anna Schroeder, Peter Wieghofer, Carmen Daems, Ori Staszewski, Lieselotte Vande Walle (UGent) , Marta Joana Costa Jordao, Mozes Sze (UGent) , Hanna-Kaisa Vikkula (UGent) , Delphine Demeestere (UGent) , Griet Van Imschoot (UGent) , Charlotte Scott (UGent) , Esther Hoste (UGent) , Amanda Gonçalves (UGent) , Martin Guilliams (UGent) , Saskia Lippens (UGent) , Claude Libert (UGent) , Roosmarijn Vandenbroucke (UGent) , Ki-Wook Kim, Steffen Jung, Zsuzsanna Callaerts-Vegh, Patrick Callaerts, Joris de Wit, Mohamed Lamkanfi (UGent) , Marco Prinz and Geert van Loo (UGent)
- 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
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8565450
- MLA
- Voet, Sofie, et al. “A20 Critically Controls Microglia Activation and Inhibits Inflammasome-Dependent Neuroinflammation.” NATURE COMMUNICATIONS, vol. 9, 2018, doi:10.1038/s41467-018-04376-5.
- APA
- Voet, S., Mc Guire, C., Hagemeyer, N., Martens, A., Schroeder, A., Wieghofer, P., … van Loo, G. (2018). A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. NATURE COMMUNICATIONS, 9. https://doi.org/10.1038/s41467-018-04376-5
- Chicago author-date
- 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. https://doi.org/10.1038/s41467-018-04376-5.
- Chicago author-date (all authors)
- Voet, Sofie, 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 Scott, Esther Hoste, Amanda Gonçalves, Martin Guilliams, Saskia Lippens, Claude Libert, Roosmarijn Vandenbroucke, Ki-Wook Kim, Steffen Jung, Zsuzsanna Callaerts-Vegh, Patrick Callaerts, Joris de Wit, Mohamed Lamkanfi, Marco Prinz, and Geert van Loo. 2018. “A20 Critically Controls Microglia Activation and Inhibits Inflammasome-Dependent Neuroinflammation.” NATURE COMMUNICATIONS 9. doi:10.1038/s41467-018-04376-5.
- 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.
- IEEE
- [1]S. Voet et al., “A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation,” NATURE COMMUNICATIONS, vol. 9, 2018.
@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 Gonçalves, 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}}, keywords = {{EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS,NF-KAPPA-B,NLRP3,INFLAMMASOME,ALZHEIMERS-DISEASE,MYELOID CELLS,CNS,MACROPHAGES,GENE,HOMEOSTASIS,ARTHRITIS}}, language = {{eng}}, pages = {{15}}, title = {{A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation}}, url = {{http://doi.org/10.1038/s41467-018-04376-5}}, volume = {{9}}, year = {{2018}}, }
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