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Title:Upper-respiratory infection triggers experimental autoimmune encephalomyelitis onset in autoimmune prone t-cell receptor transgenic mice
Author(s):Blackmore, Stephen Daniel
Advisor(s):Steelman, Andrew J.
Contributor(s):Gaskins, H. Rex; Johnson, Rodney; Loerch, Steven; Rodriguez-Zas, Sandra
Department / Program:Animal Sciences
Discipline:Animal Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Multiple Sclerosis
Experimental Autoimmune Encephalomyelitis
Abstract:Multiple Sclerosis (MS) is an autoimmune-mediated demyelinating and neurodegenerative disease of the central nervous system. Most MS patients experience a disease course characterized by periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Relapse contributes to disability but the processes that trigger relapses are poorly understood. Upper-respiratory viral infection increases the risk for relapse. Here, we tested the hypothesis that upper respiratory infection is sufficient to cause glial activation, promote immune cell trafficking to the CNS and trigger pathology in an autoimmune-prone T cell receptor transgenic mouse line. To test this hypothesis we infected 2D2 mice and monitored for symptoms of inflammatory demyelination (EAE). Clinical and histological EAE was observed in ~29.2% of infected 2D2 mice which closely resembles the incidence of upper-respiratory infection-induced relapse in MS patients. Chemokine production in brain resident glial cells, primarily astrocytes was induced by TNF and IL-1β stimulation which may assist in the trafficking of immune cells to the CNS. Furthermore, pharmacological inhibitors of JNK, ERK1/2, p38, and NF-κB modulated the levels of chemokines secreted by astrocytes in response to cytokine stimulation. Increased levels of serum IFN-γ were observed in C57BL/6 mice infected with influenza as well as increased CD4+ T-cells in the choroid plexus. Finally, we observed immunosurveillance of the brain by T-cells and CD45highCD11b+ cells in C57BL/6 mice after influenza inoculation. This immunosurveillance could prove detrimental to MS patients.
Issue Date:2016-12-05
Rights Information:Copyright 2016 Stephen Blackmore
Date Available in IDEALS:2017-03-01
Date Deposited:2016-12

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