TY - JOUR
T1 - The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes
AU - Gur, Chamutal
AU - Enk, Jonatan
AU - Weitman, Efraim
AU - Bachar, Etty
AU - Suissa, Yaron
AU - Cohen, Guy
AU - Schyr, Rachel Ben Haroush
AU - Sabanay, Helena
AU - Horwitz, Elad
AU - Glaser, Benjamin
AU - Dor, Yuval
AU - Pribluda, Ariel
AU - Hanna, Jacob H.
AU - Leibowitz, Gill
AU - Mandelboim, Ofer
PY - 2013/8/29
Y1 - 2013/8/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84883247068&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0074033
DO - 10.1371/journal.pone.0074033
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C2 - 24009765
AN - SCOPUS:84883247068
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e74033
ER -
