Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.

Patients with Type 2 diabetes (T2D) are highly susceptible to infection and have an increased incidence of some tumors, possibly due to immune system dysfunction. In the innate cellular immune system, Natural Killer (NK) lymphocytes are important effectors responsible for controlling infections and...

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Autores principales:	Jeannig Berrou, Sophie Fougeray, Marion Venot, Victor Chardiny, Jean-François Gautier, Nicolas Dulphy, Antoine Toubert, Marie-Noëlle Peraldi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/baa4daf4a218477783eaf90c155eb1a9
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spelling	oai:doaj.org-article:baa4daf4a218477783eaf90c155eb1a92021-11-18T07:47:49ZNatural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.1932-620310.1371/journal.pone.0062418https://doaj.org/article/baa4daf4a218477783eaf90c155eb1a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23638076/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Patients with Type 2 diabetes (T2D) are highly susceptible to infection and have an increased incidence of some tumors, possibly due to immune system dysfunction. In the innate cellular immune system, Natural Killer (NK) lymphocytes are important effectors responsible for controlling infections and combating tumor development. We analyzed NK cell subsets in 51 patients with long-standing T2D. Compared with healthy blood donors, diabetic patients showed a profound decrease in both NKG2D-positive NK cells (44% vs. 55.5%, P<0.01) and NKp46-positive cells (26% vs. 50%, P<0.01). Decreased expression of these receptors was associated with functional defects, such as reduced NK degranulation capacity when challenged with the tumor target cell line K562 (10.3 vs. 15.8%, P<0.05). This defect could be restored in vitro by stimulating NK cells from T2D patients with IL-15 (P<0.05). NKG2D expression was found to be negatively correlated with HBA1c level (r=-0.50; P=0.009), suggesting that sustained hyperglycemia could directly influence NK cell defects. We demonstrated that endoplasmic reticulum (ER) stress, an important mediator in diabetes-associated complications, was inducible in vitro in normal NK cells and that tunicamycin treatment resulted in a significant decrease in NKG2D expression (P<0.05). Furthermore, markers of the Unfolded Protein Response (UPR) BiP, PDI and sXBP1 mRNAs were significantly increased in NK cells from T2D patients (P<0.05, P<0.01, P<0.05, respectively), indicating that ER stress is activated in vivo through both PERK and IRE1 sensors. These results demonstrate for the first time defects in NK cell-activating receptors NKG2D and NKp46 in T2D patients, and implicate the UPR pathway as a potential mechanism. These defects may contribute to susceptibility to infections and malignancies and could be targetted therapeutically.Jeannig BerrouSophie FougerayMarion VenotVictor ChardinyJean-François GautierNicolas DulphyAntoine ToubertMarie-Noëlle PeraldiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e62418 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeannig Berrou Sophie Fougeray Marion Venot Victor Chardiny Jean-François Gautier Nicolas Dulphy Antoine Toubert Marie-Noëlle Peraldi Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
description	Patients with Type 2 diabetes (T2D) are highly susceptible to infection and have an increased incidence of some tumors, possibly due to immune system dysfunction. In the innate cellular immune system, Natural Killer (NK) lymphocytes are important effectors responsible for controlling infections and combating tumor development. We analyzed NK cell subsets in 51 patients with long-standing T2D. Compared with healthy blood donors, diabetic patients showed a profound decrease in both NKG2D-positive NK cells (44% vs. 55.5%, P<0.01) and NKp46-positive cells (26% vs. 50%, P<0.01). Decreased expression of these receptors was associated with functional defects, such as reduced NK degranulation capacity when challenged with the tumor target cell line K562 (10.3 vs. 15.8%, P<0.05). This defect could be restored in vitro by stimulating NK cells from T2D patients with IL-15 (P<0.05). NKG2D expression was found to be negatively correlated with HBA1c level (r=-0.50; P=0.009), suggesting that sustained hyperglycemia could directly influence NK cell defects. We demonstrated that endoplasmic reticulum (ER) stress, an important mediator in diabetes-associated complications, was inducible in vitro in normal NK cells and that tunicamycin treatment resulted in a significant decrease in NKG2D expression (P<0.05). Furthermore, markers of the Unfolded Protein Response (UPR) BiP, PDI and sXBP1 mRNAs were significantly increased in NK cells from T2D patients (P<0.05, P<0.01, P<0.05, respectively), indicating that ER stress is activated in vivo through both PERK and IRE1 sensors. These results demonstrate for the first time defects in NK cell-activating receptors NKG2D and NKp46 in T2D patients, and implicate the UPR pathway as a potential mechanism. These defects may contribute to susceptibility to infections and malignancies and could be targetted therapeutically.
format	article
author	Jeannig Berrou Sophie Fougeray Marion Venot Victor Chardiny Jean-François Gautier Nicolas Dulphy Antoine Toubert Marie-Noëlle Peraldi
author_facet	Jeannig Berrou Sophie Fougeray Marion Venot Victor Chardiny Jean-François Gautier Nicolas Dulphy Antoine Toubert Marie-Noëlle Peraldi
author_sort	Jeannig Berrou
title	Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
title_short	Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
title_full	Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
title_fullStr	Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
title_full_unstemmed	Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
title_sort	natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/baa4daf4a218477783eaf90c155eb1a9
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Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.

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