| First Author | Todd BP | Year | 2023 |
| Journal | Acta Neuropathol Commun | Volume | 11 |
| Issue | 1 | Pages | 134 |
| PubMed ID | 37596685 | Mgi Jnum | J:340860 |
| Mgi Id | MGI:7520985 | Doi | 10.1186/s40478-023-01635-5 |
| Citation | Todd BP, et al. (2023) Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury. Acta Neuropathol Commun 11(1):134 |
| abstractText | Accumulating evidence suggests that type I interferon (IFN-I) signaling is a key contributor to immune cell-mediated neuropathology in neurodegenerative diseases. Recently, we demonstrated a robust upregulation of type I interferon-stimulated genes in microglia and astrocytes following experimental traumatic brain injury (TBI). The specific molecular and cellular mechanisms by which IFN-I signaling impacts the neuroimmune response and neuropathology following TBI remains unknown. Using the lateral fluid percussion injury model (FPI) in adult male mice, we demonstrated that IFN alpha/beta receptor (IFNAR) deficiency resulted in selective and sustained blockade of type I interferon-stimulated genes following TBI as well as decreased microgliosis and monocyte infiltration. Molecular alteration of reactive microglia also occurred with diminished expression of genes needed for MHC class I antigen processing and presentation following TBI. This was associated with decreased accumulation of cytotoxic T cells in the brain. The IFNAR-dependent modulation of the neuroimmune response was accompanied by protection from secondary neuronal death, white matter disruption, and neurobehavioral dysfunction. These data support further efforts to leverage the IFN-I pathway for novel, targeted therapy of TBI. |
