1. Sema4A inhibits the therapeutic effect of IFN-β in EAE.
- Author
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Koda T, Okuno T, Takata K, Honorat JA, Kinoshita M, Tada S, Moriya M, Sakoda S, Mochizuki H, Kumanogoh A, and Nakatsuji Y
- Subjects
- Animals, Cell Differentiation drug effects, Cell Differentiation immunology, Drug Resistance, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental immunology, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunohistochemistry, Lymphocyte Activation immunology, Mice, Mice, Inbred C57BL, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Semaphorins pharmacology, Encephalomyelitis, Autoimmune, Experimental metabolism, Immunologic Factors pharmacology, Interferon-beta pharmacology, Lymphocyte Activation drug effects, Semaphorins metabolism
- Abstract
Approximately one-third of patients with multiple sclerosis (MS) respond poorly to interferon-beta (IFN-β) therapy. Serum Sema4A is increased in MS patients, and those who have high Sema4A do not respond to IFN-β therapy. In this study, we investigated whether recombinant Sema4A abrogates the efficacy of IFN-β in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Administration of Sema4A concurrently with IFN-β diminished the efficacy of IFN-β in EAE. These effects of Sema4A were attributed to promote Th1 and Th17 differentiation and to increase adhesive activation of T cells to endothelial cells, even in the presence of IFN-β., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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