The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes

Chamutal Gur, Jonatan Enk, Efraim Weitman, Etty Bachar, Yaron Suissa, Guy Cohen, Rachel Ben Haroush Schyr, Helena Sabanay, Elad Horwitz, Benjamin Glaser, Yuval Dor, Ariel Pribluda, Jacob H. Hanna, Gill Leibowitz, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere74033
JournalPLoS ONE
Volume8
Issue number8
DOIs
StatePublished - 29 Aug 2013

Fingerprint

Dive into the research topics of 'The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes'. Together they form a unique fingerprint.

Cite this