AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis.

AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis.

Publication date: May 03, 2021

The role of the PYHIN family member absent in melanoma 2 (AIM2), another important inflammasome sensor, in EAE remains unclear. In this study, we found that AIM2 negatively regulates the pathogenesis of EAE independent of inflammasome activation. AIM2 deficiency enhanced microglia activation and infiltration of peripheral immune cells into the CNS, thereby promoting neuroinflammation and demyelination during EAE. Mechanistically, AIM2 negatively regulates the DNA-PK-AKT3 in microglia to control neuroinflammation synergistically induced by cGAS and DNA-PK. Administration of a DNA-PK inhibitor reduced the severity of the EAE. Collectively, these findings identify a new role for AIM2 in controlling the onset of EAE. Furthermore, delineation of the underlying inflammasome-independent mechanism highlights cGAS and DNA-PK signaling as potential targets for the treatment of heterogeneous MS.

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Concepts Keywords
Dna Microglia
Encephalomyelitis AIM2
Genes Experimental autoimmune encephalomyelitis
Inflammation Inflammasome
Inhibitor Glial cells
Neuroinflammation Cytokines
Pathogenesis Branches of biology
MS
Neuroinflammation
EAE

Semantics

Type Source Name
disease MESH demyelination
pathway KEGG Melanoma
disease MESH melanoma
disease MESH inflammation
disease MESH experimental autoimmune encephalomyelitis

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