Dual role of neuronal STAT1 in encephalitis
Neuronal STAT1 phosphorylation (pSTAT1) and downstream signaling are essential for antiviral defense but can drive immune-mediated synaptic and circuit pathology when sustained.
Across viral, post-infectious, and autoimmune encephalitis, neuronal pSTAT1 functions as a context-dependent switch, linking immune activation to synaptopathy.
Chronic neuronal interferon–STAT1 signaling promotes phagocyte-mediated synaptic stripping and durable epigenetic repression of synaptic gene networks.
Brain tissue-resident memory CD8+ T cells sustain local interferon signaling, creating self-perpetuating neuroimmune niches in autoimmune encephalitis.
CNS-penetrant JAK inhibition demonstrates proof-of-principle therapeutic modulation of neuronal STAT1 signaling.
https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(26)00078-0
