Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease

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 fro...

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Autores principales: Kurnellas, Michael P., Schartner, Jill M., Fathman, C. Garrison, Jagger, Ann, Steinman, Lawrence, Rothbard, Jonathan B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144739/
https://www.ncbi.nlm.nih.gov/pubmed/25073790
http://dx.doi.org/10.1084/jem.20140107
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author Kurnellas, Michael P.
Schartner, Jill M.
Fathman, C. Garrison
Jagger, Ann
Steinman, Lawrence
Rothbard, Jonathan B.
author_facet Kurnellas, Michael P.
Schartner, Jill M.
Fathman, C. Garrison
Jagger, Ann
Steinman, Lawrence
Rothbard, Jonathan B.
author_sort Kurnellas, Michael P.
collection PubMed
description 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.
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spelling pubmed-41447392015-02-25 Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease Kurnellas, Michael P. Schartner, Jill M. Fathman, C. Garrison Jagger, Ann Steinman, Lawrence Rothbard, Jonathan B. J Exp Med Article 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. The Rockefeller University Press 2014-08-25 /pmc/articles/PMC4144739/ /pubmed/25073790 http://dx.doi.org/10.1084/jem.20140107 Text en © 2014 Kurnellas et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Kurnellas, Michael P.
Schartner, Jill M.
Fathman, C. Garrison
Jagger, Ann
Steinman, Lawrence
Rothbard, Jonathan B.
Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
title Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
title_full Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
title_fullStr Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
title_full_unstemmed Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
title_short Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
title_sort mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144739/
https://www.ncbi.nlm.nih.gov/pubmed/25073790
http://dx.doi.org/10.1084/jem.20140107
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