TY - JOUR
T1 - The AIM2 inflammasome is activated in astrocytes during the late phase of EAE
AU - Barclay, William E.
AU - Aggarwal, Nupur
AU - Elizabeth Deerhake, M.
AU - Inoue, Makoto
AU - Nonaka, Toshiaki
AU - Nozaki, Kengo
AU - Luzum, Nathan A.
AU - Miao, Edward A.
AU - Shinohara, Mari L.
N1 - Funding Information:
We appreciate Douglas Golenbock for his gift of a mutant mouse strain and for sharing unpublished data. We also appreciate Cagla Eroglu and Maria Pia Rodriguez Salazar for their advice on handling astrocytes. We appreciate Ryan Finethy for his advice on inflammasome immunostaining protocols. We also appreciate Tomoko Kadota and Amesha Crudup for their help in mouse maintenance. This study was funded to MLS by National Multiple Sclerosis Society Research Grant (RG-1801-30040), NIH (R01-NS120417, R01-AI088100) and the Chancellor’s Discovery Program Research Fund at Duke University School of Medicine.
Publisher Copyright:
Copyright: © 2022, Barclay et al.
PY - 2022/4/22
Y1 - 2022/4/22
N2 - 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.
AB - 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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U2 - 10.1172/jci.insight.155563
DO - 10.1172/jci.insight.155563
M3 - Article
C2 - 35451371
AN - SCOPUS:85128618096
SN - 2379-3708
VL - 7
JO - JCI insight
JF - JCI insight
IS - 8
M1 - e155563
ER -