PloS one, 2013-08, Vol.8 (8), p.e74033
2013
Details
- Autor(en) / Beteiligte
- Titel
- The expression of the beta cell-derived autoimmune ligand for the killer receptor nkp46 is attenuated in type 2 diabetes
- Ist Teil von
- PloS one, 2013-08, Vol.8 (8), p.e74033
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- NK cells rapidly kill tumor cells, virus infected cells and even self cells. This is mediated via killer receptors, among which NKp46 (NCR1 in mice) is prominent. We have recently demonstrated that in type 1 diabetes (T1D) NK cells accumulate in the diseased pancreas and that they manifest a hyporesponsive phenotype. In addition, we found that NKp46 recognizes an unknown ligand expressed by beta cells derived from humans and mice and that blocking of NKp46 activity prevented diabetes development. Here we investigated the properties of the unknown NKp46 ligand. We show that the NKp46 ligand is mainly located in insulin granules and that it is constitutively secreted. Following glucose stimulation the NKp46 ligand translocates to the cell membrane and its secretion decreases. We further demonstrate by using several modalities that the unknown NKp46 ligand is not insulin. Finally, we studied the expression of the NKp46 ligand in type 2 diabetes (T2D) using 3 different in vivo models and 2 species; mice and gerbils. We demonstrate that the expression of the NKp46 ligand is decreased in all models of T2D studied, suggesting that NKp46 is not involved in T2D.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0074033Titel-ID: cdi_plos_journals_1428807151
- Format
- –
- Schlagworte
- Analysis, Animal models, Animals, Antigens, Ly - genetics, Antigens, Ly - metabolism, Autoimmunity - genetics, Beta cells, Biology, Cancer, Cytotoxicity, Developmental biology, Dextrose, Diabetes, Diabetes mellitus, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2 - genetics, Diabetes Mellitus, Type 2 - immunology, Diabetes Mellitus, Type 2 - metabolism, Endocrinology, Gene Expression, Gene Expression Regulation - drug effects, Glucose, Immunology, Insulin, Insulin - metabolism, Insulin Secretion, Insulin-Secreting Cells - immunology, Insulin-Secreting Cells - metabolism, Internal medicine, Killer cells, Laboratories, Leptin - administration & dosage, Ligands, Male, Medical research, Medicine, Metabolism, Mice, Natural Cytotoxicity Triggering Receptor 1 - genetics, Natural Cytotoxicity Triggering Receptor 1 - metabolism, Pancreas, Pancreatic beta cells, Pathogens, Protein Binding, Psammomys obesus, Receptors, Secretion, Tumor cells, Type 1 diabetes, Type 2 diabetes, Viruses