A proinsulin 74-90-derived protease-resistant, altered peptide ligand increases TGF-beta 1 secretion in PBMC from patients with type 1 diabetes mellitus
| Autor: | Timo Burster, Andreas Spyrantis, Silke Rosinger, David Palesch, Denise van Aalst, Hubert Kalbacher, Bernhard O. Boehm, Fang Zou |
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| Rok vydání: | 2010 |
| Předmět: |
endocrine system
endocrine system diseases Regulatory T cell medicine.medical_treatment T-Lymphocytes Immunology Molecular Sequence Data Cell Separation Biology Ligands Lymphocyte Activation Autoantigens Epitope Transforming Growth Factor beta1 Immune system Antigen medicine Immunology and Allergy Humans Secretion IL-2 receptor Amino Acid Sequence Proinsulin nutritional and metabolic diseases Cell Biology Flow Cytometry Cytokine medicine.anatomical_structure Diabetes Mellitus Type 1 Cancer research Leukocytes Mononuclear hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of leukocyte biology. 87(5) |
| ISSN: | 1938-3673 |
| Popis: | Proinsulin-based protease-resistant altered peptide ligands modulate proinsulin-reactive T cells to secret the anti-inflammatory cytokine TGF-β1. 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 proinsulin74–90-derived APL using a CS-directed amino acid modification approach. These prAPL activated TGF-β1 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-β1. Thus, the use of prAPL is a promising tool to mitigate autoaggressive T cells. |
| Databáze: | OpenAIRE |
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