RT Journal Article SR Electronic T1 Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection Following Traumatic Brain Injury JF eneuro JO eneuro FD Society for Neuroscience SP ENEURO.0128-15.2016 DO 10.1523/ENEURO.0128-15.2016 VO 3 IS 1 A1 Ila P. Karve A1 Moses Zhang A1 Mark Habgood A1 Tony Frugier A1 Kate M. Brody A1 Maithili Sashindranath A1 C. Joakim Ek A1 Stephane Chappaz A1 Ben T. Kile A1 David Wright A1 Hong Wang A1 Leigh Johnston A1 Maria Daglas A1 Robert C. Ates A1 Robert L. Medcalf A1 Juliet M. Taylor A1 Peter J. Crack YR 2016 UL http://www.eneuro.org/content/3/1/ENEURO.0128-15.2016.abstract 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.