Unlocking microglia pyroptosis in a model of type I interferon-driven neuroinflammation: lessons from Rnaset2^-/- mice.

ABSTRACT: RNaseT2-deficient cystic leukoencephalopathy (CLE) presents with severe psychomotor retardation, cystic brain lesions, white matter alterations, and cerebral atrophy. The Rnaset2^-/- mouse mirrors key features of this disease and represents the first murine model with a distinct neurological phenotype for type I interferonopathies. Rnaset2^-/- mice exhibit activated microglia, perivascular monocyte and CD8 + T cell infiltration, and hippocampal accentuated atrophy. However, the mechanisms linking interferon-driven neuroinflammation to neurodegeneration remain unclear, underscoring the need to clarify which molecular processes contribute to tissue injury in a time-dependent manner. We found a sustained upregulation of interferon-stimulated genes (IRF9, RIG-I) over three

SUBMITTER: Wendland K 

PROVIDER: S-EPMC12848040 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature