ArticlePloS one2013
Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Natural killer cell levels in adults living with type 2 diabetes: a systematic review and meta-analysis of clinical studies.BMC immunology · 2020Pooled it
- Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: AGut and liver · 2024Trial
- Relationship between natural killer cell activity and glucose control in patients with type 2 diabetes and prediabetes.Journal of diabetes investigation · 2019Trial
- The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peripheral Inflammatory Networks.Cellular and molecular neurobiology · 2026Review
- The impact of chronic comorbidities on cancer immunoediting: challenges and opportunities for immunotherapies.Frontiers in immunology · 2026Review
- Immunocytes Play a Crucial Role as Mediators in the Protective Effects of D-β-Hydroxybutyrate Dehydrogenase 1 against Type 2 Diabetes Mellitus: A Mendelian Randomization StudyEndocrine, metabolic & immune disorders drug targets · 2026Article
- A Retrospective Real-World Study: The Efficacy and Safety of Immune Checkpoint Inhibitors Combined with Chemoradiotherapy in Limited-Stage Small Cell Lung Cancer.Oncology research · 2026Article
- PET Imaging of Diabetes-Induced Alterations in Metabolism and Immune Activation.Molecular imaging and biology · 2025Article
- Enhanced M2 Polarization of Retinal Microglia in Streptozotocin-Induced Diabetic Mice upon Autoimmune Stimulation.Biomedicines · 2025Article
- Immune Dysregulation Connecting Type 2 Diabetes and Cardiovascular Complications.Life (Basel, Switzerland) · 2025Review
- Dysregulation of NK cell subsets and phenotypes in COVID-19 patients with comorbid type 2 diabetes.Clinical science (London, England : 1979) · 2025Article
- Depletion of natural killer cells enhances wound healing in diabetic mice.Journal of leukocyte biology · 2025Article
- Exploring the Link Between Diabetes, Herpes Zoster, and Post-Herpetic Neuralgia: Insights From Mendelian Randomization.Journal of pain research · 2025Article
- Article
- Macrophages and T cells in metabolic disorder-associated cancers.Nature reviews. Cancer · 2024Review
- The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.Medicina (Kaunas, Lithuania) · 2024Review
- Impact of hyperglycemia on immune cell function: a comprehensive review.Diabetology international · 2024Review
- Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Multifaceted Roles of Vitamin D for Diabetes: From Immunomodulatory Functions to Metabolic Regulations.Nutrients · 2024Review
- Effects of motivational interviewing intervention on psychological status, compliance behavior and quality of life of patients with malignant tumor combined with diabetes mellitus.Pakistan journal of medical sciences · 2024Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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