Journal article
Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury
Acta neuropathologica communications, Vol.11(1), 134
08/18/2023
DOI: 10.1186/s40478-023-01635-5
PMCID: PMC10436463
PMID: 37596685
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. 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.
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 R. 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
- Journal article
- Publication Details
- Acta neuropathologica communications, Vol.11(1), 134
- DOI
- 10.1186/s40478-023-01635-5
- PMID
- 37596685
- PMCID
- PMC10436463
- NLM abbreviation
- Acta Neuropathol Commun
- ISSN
- 2051-5960
- eISSN
- 2051-5960
- Publisher
- BioMed Central
- Grant note
- K08NS110829; 5P50HD103556; R01AI042767; R01AI114543; R01AI167847 / ;
- Language
- English
- Date published
- 08/18/2023
- Academic Unit
- Neurology; Psychiatry; Critical Care; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics); Iowa Institute of Human Genetics
- Record Identifier
- 9984455467902771
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