| First Author | Khorooshi R | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 2 | Pages | 1258-64 |
| PubMed ID | 20562259 | Mgi Jnum | J:161928 |
| Mgi Id | MGI:4462071 | Doi | 10.4049/jimmunol.0901753 |
| Citation | Khorooshi R, et al. (2010) Injury-induced type I IFN signaling regulates inflammatory responses in the central nervous system. J Immunol 185(2):1258-64 |
| abstractText | 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. |
