A proinsulin 74-90-derived protease-resistant, altered peptide ligand increases TGF-beta 1 secretion in PBMC from patients with type 1 diabetes mellitus

Denise van Aalst, Hubert Kalbacher, David Palesch, Fang Zou, Andreas Spyrantis, Silke Rosinger, Bernhard O Boehm, Timo Burster

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Proinsulin is a major diabetes-associated autoantigen. APL have been shown to manipulate the immune response of T cells. Here, we generated a lysosomal protease-resistant proinsulin 74-90-derived APL using a CS-directed amino acid modification approach. These prAPL activated TGF-beta 1 secretion in proinsulin-reactive T cells from PBMC of patients with T1D. We provide evidence that proinsulin-derived prAPL modulate the cytokine signature of proinsulin-reactive T cells at a micromolar range by increasing anti-inflammatory cytokines, including TGF-beta 1. Thus, the use of prAPL is a promising tool to mitigate autoaggressive T cells.

Original languageEnglish
Pages (from-to)943-8
Number of pages6
JournalJournal of Leukocyte Biology
Volume87
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Transforming Growth Factor beta1
Proinsulin
Type 1 Diabetes Mellitus
Peptide Hydrolases
Ligands
Peptides
T-Lymphocytes
Cytokines
Autoantigens
Anti-Inflammatory Agents
Amino Acids

Keywords

  • Amino Acid Sequence
  • Autoantigens
  • Cell Separation
  • Diabetes Mellitus, Type 1
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear
  • Ligands
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Proinsulin
  • T-Lymphocytes
  • Transforming Growth Factor beta1
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

A proinsulin 74-90-derived protease-resistant, altered peptide ligand increases TGF-beta 1 secretion in PBMC from patients with type 1 diabetes mellitus. / van Aalst, Denise; Kalbacher, Hubert; Palesch, David; Zou, Fang; Spyrantis, Andreas; Rosinger, Silke; Boehm, Bernhard O; Burster, Timo.

In: Journal of Leukocyte Biology, Vol. 87, No. 5, 05.2010, p. 943-8.

Research output: Contribution to journalArticle

van Aalst, Denise ; Kalbacher, Hubert ; Palesch, David ; Zou, Fang ; Spyrantis, Andreas ; Rosinger, Silke ; Boehm, Bernhard O ; Burster, Timo. / A proinsulin 74-90-derived protease-resistant, altered peptide ligand increases TGF-beta 1 secretion in PBMC from patients with type 1 diabetes mellitus. In: Journal of Leukocyte Biology. 2010 ; Vol. 87, No. 5. pp. 943-8.
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AU - Zou, Fang

AU - Spyrantis, Andreas

AU - Rosinger, Silke

AU - Boehm, Bernhard O

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