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
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Adoptive Transfer
- Adult
- Amyloid / immunology*
- Amyloid / therapeutic use*
- Animals
- Encephalomyelitis, Autoimmune, Experimental / genetics
- Encephalomyelitis, Autoimmune, Experimental / immunology*
- Encephalomyelitis, Autoimmune, Experimental / therapy*
- Female
- Gene Expression
- Humans
- Immunosuppressive Agents / therapeutic use
- Interferon Type I / metabolism
- Interferon-gamma / metabolism
- Interleukin-6 / metabolism
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Peptide Fragments / immunology*
- Peptide Fragments / therapeutic use*
- Th1 Cells / immunology
- Th17 Cells / immunology
- Tumor Necrosis Factor-alpha / metabolism
- tau Proteins / immunology
- tau Proteins / therapeutic use
Substances
- Amyloid
- Immunosuppressive Agents
- Interferon Type I
- Interleukin-6
- Peptide Fragments
- Tumor Necrosis Factor-alpha
- tau Proteins
- Interferon-gamma