Regulation of Cathepsin G Reduces the Activation of Proinsulin-Reactive T Cells from Type 1 Diabetes Patients

Simple item page
dc.contributor.authorZou, Fang
dc.contributor.authorSchafer, Nadja
dc.contributor.authorPalesch, David
dc.contributor.authorBrucken, Ruth
dc.contributor.authorBeck, Alexander
dc.contributor.authorSienczyk, Marcin
dc.contributor.authorKalbacher, Hubert
dc.contributor.authorSun, ZiLin
dc.contributor.authorBoehm, Bernhard O.
dc.contributor.authorBurster, Timo
dc.contributor.editorHerrath, Matthias G.
dc.date.accessioned2018-08-20T03:23:38Z
dc.date.available2018-08-20T03:23:38Z
dc.date.issued2011-08-05
dc.description.abstractAutoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major histocompatibility complex (MHC) class II molecules for CD4+ T cell inspection. However, the processing and presentation of proinsulin by antigen-presenting cells (APC) in humans is only partially understood. Here we demonstrate that the processing of proinsulin by B cell or myeloid dendritic cell (mDC1)-derived lysosomal cathepsins resulted in several proinsulin-derived intermediates. These intermediates were similar to those obtained using purified CatG and, to a lesser extent, CatD, S, and V in vitro. Some of these intermediates polarized T cell activation in peripheral blood mononuclear cells (PBMC) from T1D patients indicative for naturally processed T cell epitopes. Furthermore, CatG activity was found to be elevated in PBMC from T1D patients and abrogation of CatG activity resulted in functional inhibition of proinsulin-reactive T cells. Our data suggested the notion that CatG plays a critical role in proinsulin processing and is important in the activation process of diabetogenic T cells.en_US
dc.identifier.citationZou F, Scha¨fer N, Palesch D, Bru¨ cken R, Beck A, et al. (2011) Regulation of Cathepsin G Reduces the Activation of Proinsulin-Reactive T Cells from Type 1 Diabetes Patients. PLoS ONE 6(8): e22815. doi:10.1371/journal.pone.0022815en_US
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/3386
dc.language.isoenen_US
dc.publisherPLoS ONEen_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectDiabetes Patientsen_US
dc.subjectDiabetesen_US
dc.titleRegulation of Cathepsin G Reduces the Activation of Proinsulin-Reactive T Cells from Type 1 Diabetes Patientsen_US
dc.typeArticleen_US
workflow.import.sourcescience

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Regulation of Cathepsin G Reduces the Activation of.pdf
Size:
845.46 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
6 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Articles