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

doi:10.1371/journal.pone.0074033

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 journal › Article › peer-review

16 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 language	American English
Article number	e74033
Journal	PLoS ONE
Volume	8
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0074033
State	Published - 29 Aug 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0074033

Cite this

Gur, C., Enk, J., Weitman, E., Bachar, E., Suissa, Y., Cohen, G., Schyr, R. B. H., Sabanay, H., Horwitz, E., Glaser, B., Dor, Y., Pribluda, A., Hanna, J. H., Leibowitz, G., & Mandelboim, O. (2013). The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes. PLoS ONE, 8(8), Article e74033. https://doi.org/10.1371/journal.pone.0074033

@article{c83c91cbd6d04010a798c3cb5f71e274,

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

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.",

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

year = "2013",

month = aug,

day = "29",

doi = "10.1371/journal.pone.0074033",

language = "American English",

volume = "8",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "8",

}

Gur, C, Enk, J, Weitman, E, Bachar, E, Suissa, Y, Cohen, G, Schyr, RBH, Sabanay, H, Horwitz, E, Glaser, B, Dor, Y, Pribluda, A, Hanna, JH, Leibowitz, G & Mandelboim, O 2013, 'The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes', PLoS ONE, vol. 8, no. 8, e74033. https://doi.org/10.1371/journal.pone.0074033

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

M3 - Article

C2 - 24009765

AN - SCOPUS:84883247068

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e74033

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this