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 Libert; Roos E. Vandenbroucke; Ki-Wook Kim; Steffen Jung; Zsuzsanna Callaerts-Vegh; Patrick Callaerts; Joris de Wit; Mohamed Lamkanfi; Marco Prinz; Geert van Loo

doi:https://doi.org/10.1038/s41467-018-04376-5

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

Department of Systems Immunology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	2036
Number of pages	15
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04376-5
State	Published - 23 May 2018

All Science Journal Classification (ASJC) codes

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

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Voet, S., Mc Guire, C., Hagemeyer, N., Martens, A., Schroeder, A., Wieghofer, P., Daems, C., Staszewski, O., Walle, L. V., Jordao, M. J. C., Sze, M., Vikkula, H-K., Demeestere, D., Van Imschoot, G., Scott, C. L., Hoste, E., Goncalves, A., Guilliams, M., Lippens, S., ... van Loo, G. (2018). A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. Nature Communications, 9(1), Article 2036. https://doi.org/10.1038/s41467-018-04376-5

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title = "A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = may,

day = "23",

doi = "https://doi.org/10.1038/s41467-018-04376-5",

language = "الإنجليزيّة",

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Voet, S, Mc Guire, C, Hagemeyer, N, Martens, A, Schroeder, A, Wieghofer, P, Daems, C, Staszewski, O, Walle, LV, Jordao, MJC, Sze, M, Vikkula, H-K, Demeestere, D, Van Imschoot, G, Scott, CL, Hoste, E, Goncalves, A, Guilliams, M, Lippens, S, Libert, C, Vandenbroucke, RE, Kim, K-W, Jung, S, Callaerts-Vegh, Z, Callaerts, P, de Wit, J, Lamkanfi, M, Prinz, M & van Loo, G 2018, 'A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation', Nature Communications, vol. 9, no. 1, 2036. https://doi.org/10.1038/s41467-018-04376-5

TY - JOUR

T1 - A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation

AU - Voet, Sofie

AU - Mc Guire, Conor

AU - Hagemeyer, Nora

AU - Martens, Arne

AU - Schroeder, Anna

AU - Wieghofer, Peter

AU - Daems, Carmen

AU - Staszewski, Ori

AU - Walle, Lieselotte Vande

AU - Jordao, Marta Joana Costa

AU - Sze, Mozes

AU - Vikkula, Hanna-Kaisa

AU - Demeestere, Delphine

AU - Van Imschoot, Griet

AU - Scott, Charlotte L.

AU - Hoste, Esther

AU - Goncalves, Amanda

AU - Guilliams, Martin

AU - Lippens, Saskia

AU - Libert, Claude

AU - Vandenbroucke, Roos E.

AU - Kim, Ki-Wook

AU - Jung, Steffen

AU - Callaerts-Vegh, Zsuzsanna

AU - Callaerts, Patrick

AU - de Wit, Joris

AU - Lamkanfi, Mohamed

AU - Prinz, Marco

AU - van Loo, Geert

PY - 2018/5/23

Y1 - 2018/5/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047762349&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s41467-018-04376-5

DO - https://doi.org/10.1038/s41467-018-04376-5

M3 - مقالة

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2036

ER -

A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation

Abstract

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