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The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.

Publication ,  Journal Article
Barclay, WE; Aggarwal, N; Deerhake, ME; Inoue, M; Nonaka, T; Nozaki, K; Luzum, NA; Miao, EA; Shinohara, ML
Published in: JCI insight
April 2022

Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here, we used multiple genetically modified mouse models to monitor activated inflammasomes in situ based on oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC) in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation during EAE was dependent on absent in melanoma 2 (AIM2), but low IL-1β release and no significant signs of cell death were found. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.

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Published In

JCI insight

DOI

EISSN

2379-3708

ISSN

2379-3708

Publication Date

April 2022

Volume

7

Issue

8

Start / End Page

e155563

Related Subject Headings

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice
  • Melanoma
  • Inflammation
  • Inflammasomes
  • Encephalomyelitis, Autoimmune, Experimental
  • Disease Models, Animal
  • DNA-Binding Proteins
  • Astrocytes
  • Animals
 

Citation

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ICMJE
MLA
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Barclay, W. E., Aggarwal, N., Deerhake, M. E., Inoue, M., Nonaka, T., Nozaki, K., … Shinohara, M. L. (2022). The AIM2 inflammasome is activated in astrocytes during the late phase of EAE. JCI Insight, 7(8), e155563. https://doi.org/10.1172/jci.insight.155563
Barclay, William E., Nupur Aggarwal, M Elizabeth Deerhake, Makoto Inoue, Toshiaki Nonaka, Kengo Nozaki, Nathan A. Luzum, Edward A. Miao, and Mari L. Shinohara. “The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.JCI Insight 7, no. 8 (April 2022): e155563. https://doi.org/10.1172/jci.insight.155563.
Barclay WE, Aggarwal N, Deerhake ME, Inoue M, Nonaka T, Nozaki K, et al. The AIM2 inflammasome is activated in astrocytes during the late phase of EAE. JCI insight. 2022 Apr;7(8):e155563.
Barclay, William E., et al. “The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.JCI Insight, vol. 7, no. 8, Apr. 2022, p. e155563. Epmc, doi:10.1172/jci.insight.155563.
Barclay WE, Aggarwal N, Deerhake ME, Inoue M, Nonaka T, Nozaki K, Luzum NA, Miao EA, Shinohara ML. The AIM2 inflammasome is activated in astrocytes during the late phase of EAE. JCI insight. 2022 Apr;7(8):e155563.

Published In

JCI insight

DOI

EISSN

2379-3708

ISSN

2379-3708

Publication Date

April 2022

Volume

7

Issue

8

Start / End Page

e155563

Related Subject Headings

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice
  • Melanoma
  • Inflammation
  • Inflammasomes
  • Encephalomyelitis, Autoimmune, Experimental
  • Disease Models, Animal
  • DNA-Binding Proteins
  • Astrocytes
  • Animals