title: Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease.
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.
authors: Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Michael P
authors: MP
authors: Kurnellas
authors: Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Jill M
authors: JM
authors: Schartner
authors: Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: C Garrison
authors: CG
authors: Fathman
authors: Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Ann
authors: A
authors: Jagger
authors: Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305 steinman@stanford.edu.
authors: Lawrence
authors: L
authors: Steinman
authors: Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305 Department of Neurology and Neurological Sciences and Department of Medicine, Division of Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Jonathan B
authors: JB
authors: Rothbard
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000682:Amyloid / Q000276:immunology* / Q000627:therapeutic use*; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007370:Interferon Type I / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016875:tau Proteins / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000682:Amyloid; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D007371:Interferon-gamma