RRC ID 6044
Author Khorooshi R, Owens T.
Title Injury-induced type I IFN signaling regulates inflammatory responses in the central nervous system.
Journal J. Immunol.
Abstract Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I IFNs signal through a receptor (IFNAR), which involves activation of IFN regulatory factor (IRF)9, leading to the induction of IFN-stimulated genes including IRF7, that in turn enhances the induction of type I IFN. Axonal transection induced upregulation of IRF7 and IRF9 in hippocampus. Induction of IRF7 and IRF9 mRNAs was IFNAR dependent. Double-labeling immunofluorescence showed that IRF7 selectively was induced in Mac-1/CD11b(+) macrophages/microglia in hippocampus after axonal transection. IRF7 mRNA was also detected in microglia sorted by flow cytometry. Lack of type I IFN signaling resulted in increased leukocyte infiltration into the lesion-reactive hippocampus. Axonal lesion-induced CXCL10 gene expression was abrogated, whereas matrix metalloproteinase 9 mRNA was elevated in IFNAR-deficient mice. Our findings point to a role for type I IFN signaling in regulation of CNS response to sterile injury.
Volume 185(2)
Pages 1258-64
Published 2010-7-15
DOI 10.4049/jimmunol.0901753
PII jimmunol.0901753
PMID 20562259
MeSH Animals Blotting, Western Brain Injuries / immunology CD11b Antigen / analysis Central Nervous System / immunology* Central Nervous System / metabolism Central Nervous System / pathology Chemokine CXCL10 / genetics Chemokine CXCL10 / immunology Chemokine CXCL10 / metabolism Female Glial Fibrillary Acidic Protein / analysis Hippocampus / injuries Hippocampus / metabolism Immunohistochemistry Inflammation / genetics Inflammation / immunology* Inflammation / metabolism Inflammation Mediators / immunology Inflammation Mediators / metabolism Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / immunology Interferon Regulatory Factor-7 / metabolism Interferon Type I / immunology* Leukocytes / immunology Leukocytes / pathology Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / immunology Matrix Metalloproteinase 9 / metabolism Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Receptor, Interferon alpha-beta / genetics Receptor, Interferon alpha-beta / immunology Receptor, Interferon alpha-beta / metabolism Reverse Transcriptase Polymerase Chain Reaction STAT1 Transcription Factor / genetics STAT1 Transcription Factor / immunology STAT1 Transcription Factor / metabolism Signal Transduction / immunology*
IF 4.539
Times Cited 41
Mice IRF-7 knockout mice C57BL/6J