Epstein–Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis

• Published in: Journal of neuroimmunology Vol. 254; no. 1; pp. 110 - 116
• Main Authors: Tirotta, Emanuele, Duncker, Patrick, Oak, Jean, Klaus, Suzi, Tsukamoto, Michelle R, Gov, Lanny, Lane, Thomas E
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2013
• Subjects: Allergy and Immunology; Animals; Antigens, CD - metabolism; CD8 Antigens - metabolism; Coronavirus Infections - complications; Cytokines; Cytokines - genetics; Cytokines - metabolism; Demyelination; Disease Models, Animal; Encephalomyelitis - etiology; Encephalomyelitis - immunology; Encephalomyelitis - mortality; Encephalomyelitis - pathology; Flow Cytometry; Gene Expression Regulation, Viral - genetics; Glial Fibrillary Acidic Protein - metabolism; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Minor Histocompatibility Antigens; Neuroinflammation; Neurology; Receptors, Cytokine - deficiency; Receptors, Cytokine - metabolism; RNA, Messenger - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - virology; Time Factors; Virus; Virus; Neuroinflammation; Cytokines; Demyelination
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2012.10.005

Abstract Epstein–Barr virus-induced gene 3 (EBI3) associates with p28 and p35 to form the immunomodulatory cytokines IL-27 and IL-35, respectively. Infection of EBI3 −/− mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality that was not associated with impaired ability to control viral replication but enhanced T cell and macrophage infiltration into the CNS. IFN-γ secretion from virus-specific CD4 + and CD8 + T cells isolated from infected EBI3 −/− mice was augmented while IL-10 expression muted in comparison to infected WT mice. These data demonstrate a regulatory role for EBI3-associated cytokines in controlling host responses following CNS viral infection.