Preprint
Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury
bioRxiv
Cold Spring Harbor Laboratory
06/07/2023
DOI: 10.1101/2023.06.06.543774
PMCID: PMC10274693
PMID: 37333385
Abstract
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 α/β 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. Phenotypic alteration of reactive microglia also occurred with diminished expression of molecules 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.
Details
- Title: Subtitle
- Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury
- Creators
- Brittany P. Todd - University of IowaZili Luo - University of IowaNoah Gilkes - University of IowaMichael S. Chimenti - University of IowaZeru Peterson - University of IowaMadison Mix - University of IowaJohn T. Harty - University of IowaThomas Nickl-Jockschat - University of IowaPolly J. Ferguson - University of IowaAlexander G. Bassuk - University of IowaElizabeth A. Newell - University of Iowa
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- Publisher
- Cold Spring Harbor Laboratory
- DOI
- 10.1101/2023.06.06.543774
- PMID
- 37333385
- PMCID
- PMC10274693
- Language
- English
- Date posted
- 06/07/2023
- Academic Unit
- Critical Care; Rheumatology, Allergy, and Immunology; Pathology; Neuroscience and Pharmacology; Iowa Institute of Human Genetics; Neurology; Iowa Neuroscience Institute; Stead Family Department of Pediatrics; Psychiatry; Neurology (Pediatrics)
- Record Identifier
- 9984436458602771
Metrics
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