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

Journal of Leukocyte Biology
Denise van AalstTimo Burster

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.

References

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Citations

May 15, 2015·International Reviews of Immunology·Evan L SauerJudith M Greer
Jun 19, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Menno van LummelBart O Roep

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