Abstract
Amyloid fibrils composed of peptides as short as six amino acids are effective therapeutics for experimental autoimmune encephalomyelitis (EAE). Immunosuppression arises from at least two pathways: (1) expression of type 1 IFN by pDCs, which were induced by neutrophil extracellular traps arising from the endocytosis of the fibrils; and (2) the reduced expression of IFN-γ, TNF, and IL-6. The two independent pathways stimulated by the fibrils can act in concert to be immunosuppressive in Th1 indications, or in opposition, resulting in inflammation when Th17 T lymphocytes are predominant. The generation of type 1 IFN can be minimized by using polar, nonionizable, amyloidogenic peptides, which are effective in both Th1 and Th17 polarized EAE.
© 2014 Kurnellas et al.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Adult
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Amyloid / immunology*
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Amyloid / therapeutic use*
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Animals
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / therapy*
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Female
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Gene Expression
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Humans
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Immunosuppressive Agents / therapeutic use
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Interferon Type I / metabolism
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Interferon-gamma / metabolism
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Interleukin-6 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Peptide Fragments / immunology*
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Peptide Fragments / therapeutic use*
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Th1 Cells / immunology
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Th17 Cells / immunology
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Tumor Necrosis Factor-alpha / metabolism
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tau Proteins / immunology
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tau Proteins / therapeutic use
Substances
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Amyloid
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Immunosuppressive Agents
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Interferon Type I
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Interleukin-6
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Peptide Fragments
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Tumor Necrosis Factor-alpha
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tau Proteins
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Interferon-gamma