title: Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis.
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.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, United States.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Tirotta
authors.forename: Patrick
authors.initials: P
authors.lastname: Duncker
authors.forename: Jean
authors.initials: J
authors.lastname: Oak
authors.forename: Suzi
authors.initials: S
authors.lastname: Klaus
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Tsukamoto
authors.forename: Lanny
authors.initials: L
authors.lastname: Gov
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018352:Coronavirus Infections / Q000150:complications*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000473:pathology; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; D016207:Cytokines; C499601:Ebi3 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D016753:Interleukin-10; D007371:Interferon-gamma