PT - JOURNAL ARTICLE AU - Karve, Ila P. AU - Zhang, Moses AU - Habgood, Mark AU - Frugier, Tony AU - Brody, Kate M. AU - Sashindranath, Maithili AU - Ek, C. Joakim AU - Chappaz, Stephane AU - Kile, Ben T. AU - Wright, David AU - Wang, Hong AU - Johnston, Leigh AU - Daglas, Maria AU - Ates, Robert C. AU - Medcalf, Robert L. AU - Taylor, Juliet M. AU - Crack, Peter J. TI - Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection Following Traumatic Brain Injury AID - 10.1523/ENEURO.0128-15.2016 DP - 2016 Jan 01 TA - eneuro PG - ENEURO.0128-15.2016 VI - 3 IP - 1 4099 - http://www.eneuro.org/content/3/1/ENEURO.0128-15.2016.short 4100 - http://www.eneuro.org/content/3/1/ENEURO.0128-15.2016.full SO - eneuro2016 Jan 01; 3 AB - Type-1 interferons (IFNs) are pleiotropic cytokines that signal through the type-1 IFN receptor (IFNAR1). Recent literature has implicated the type-1 IFNs in disorders of the CNS. In this study, we have investigated the role of type-1 IFNs in neuroinflammation following traumatic brain injury (TBI). Using a controlled cortical impact model, TBI was induced in 8- to 10-week-old male C57BL/6J WT and IFNAR1−/− mice and brains were excised to study infarct volume, inflammatory mediator release via quantitative PCR analysis and immune cell profile via immunohistochemistry. IFNAR1−/− mice displayed smaller infarcts compared with WT mice after TBI. IFNAR1−/− mice exhibited an altered anti-inflammatory environment compared with WT mice, with significantly reduced levels of the proinflammatory mediators TNFα, IL-1β and IL-6, an up-regulation of the anti-inflammatory mediator IL-10 and an increased activation of resident and peripheral immune cells after TBI. WT mice injected intravenously with an anti-IFNAR1 blocking monoclonal antibody (MAR1) 1 h before, 30 min after or 30 min and 2 d after TBI displayed significantly improved histological and behavioral outcome. Bone marrow chimeras demonstrated that the hematopoietic cells are a peripheral source of type-1 IFNs that drives neuroinflammation and a worsened TBI outcome. Type-1 IFN mRNA levels were confirmed to be significantly altered in human postmortem TBI brains. Together, these data demonstrate that type-1 IFN signaling is a critical pathway in the progression of neuroinflammation and presents a viable therapeutic target for the treatment of TBI.