Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes

Hao, Juan; Xiao, Yang; Zheng, Peilin; Zhou, Wenbin; Wang, Yanfei; Huang, Gan; Xu, Aimin; Zhang, Zhou

doi:10.1002/dmrr.3064

Cited by 53 publications

(70 citation statements)

References 36 publications

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“…Neutrophils are the first-line immune cells involved in inflammation, and circulating neutrophil counts are moderately increased in type 2 diabetes [3,7]. However, the role of neutrophils in the pathogenesis of type 2 diabetes is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophils are the most abundant type of white blood cell and are reported as active players in inflammation of obesity-related insulin resistance [2]. Additionally, neutrophil count, a marker of subclinical inflammation, has been shown to significantly increase in type 2 diabetes compared with healthy subjects [3][4][5]. Neutrophil-lymphocyte ratio significantly increases in prediabetes and diabetes and may be a predictive marker for prediabetes and diabetes mellitus [6].…”

Section: Introductionmentioning

confidence: 99%

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Abnormal Peripheral Neutrophil Transcriptome in Newly Diagnosed Type 2 Diabetes Patients

Lin

Zhou

Wang

et al. 2020

Journal of Diabetes Research

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Aim. There are increasing evidence demonstrating that neutrophil-mediated inflammation plays a role in the etiology of type 2 diabetes. However, the molecular mechanisms by which neutrophils contribute to type 2 diabetes remain largely unknown. The aim of the present work was to identify possible changes in circulating neutrophils to better elucidate neutrophil involvement in human type 2 diabetes. Methods. Patients newly diagnosed with type 2 diabetes (n=5) and age- and sex-matched healthy controls (n=5) were recruited. Neutrophils were purified from type 2 diabetes patients and controls, and RNA sequencing (RNA-seq) was used for comprehensive transcriptome analysis. Differentially expressed genes (DEGs) were screened, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. Real-time polymerase chain reaction (qPCR) was used for validation in external samples of type 2 diabetes patients (n=8) and healthy controls (n=8). Results. Gene expression analysis showed that, compared with neutrophils from healthy controls, there were 1990 upregulated DEGs and 1314 downregulated DEGs in neutrophils from type 2 diabetes patients. GO analysis demonstrated that the DEGs were mainly involved in myeloid leukocyte activation, T cell activation, adaptive immunity, and cytokine production. The top 20 enriched KEGG pathways included the cytokine-cytokine receptor interaction pathway, NF-κB signaling pathway, cell adhesion molecules, and chemokine signaling pathway. Furthermore, qPCR of genes related to neutrophil activation revealed that the expression of SELL, SELP, CXCR1, and S100A8 was significantly increased in neutrophils from type 2 diabetes patients compared with that in neutrophils from controls. Conclusions. Our study reveals an abnormal activation of circulating neutrophils at the transcriptome level in type 2 diabetes patients. These findings suggest a potential involvement of neutrophil dysfunction in the pathologic process of type 2 diabetes and provide insight into potential therapeutic targets for type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abnormal Peripheral Neutrophil Transcriptome in Newly Diagnosed Type 2 Diabetes Patients

Lin

Zhou

Wang

et al. 2020

Journal of Diabetes Research

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“…Older studies have shown that in T1DM patients, there is an increase in neutrophil counts compared to healthy individuals [38,39]. Recent researches described a decrease in circulating neutrophil numbers in T1DM patients in comparison with nondiabetics [40,41]. Impairment in neutrophil yield and maturation in bone marrow, increase in peripheral neutrophil consumption, and/or tissue sequestration could explain this reduction in blood neutrophil counts observed in T1DM [42].…”

Section: Impaired Neutrophil Migration In Diabetesmentioning

confidence: 99%

“…This divergence between studies can be attributed to differences between ethnic groups and the discovery of the existence of various stages of DM [43]. While in T1DM, the data about circulating neutrophil counts are still controversial, most of the studies Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes DOI: http://dx.doi.org/10.5772/intechopen.86600 described that in T2DM patients, there is an increase in the number of neutrophils in circulation in comparison to healthy individuals [40,44]. This neutrophilia was related to elevation in the circulation levels of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, and CRP, a known marker of inflammation [45].…”

Section: Impaired Neutrophil Migration In Diabetesmentioning

confidence: 99%

“…Regarding migration, in vitro studies described a reduction in CXCL8/IL-8, platelet-activating factor (PAF), or N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis of neutrophils from T1DM or T2DM patients compared to cells from healthy subjects [40,46]. In situ evaluation of chemotaxis toward fMLP using T1DM rat neutrophils also revealed a deficiency in migration.…”

Section: Impaired Neutrophil Migration In Diabetesmentioning

confidence: 99%

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Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes

Insuela¹,

Coutinho²,

Martins³

et al. 2020

Cells of the Immune System

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Diabetes mellitus is a highly prevalent noncommunicable disease globally. One of the main complications of diabetes is the increased susceptibility to bacterial infection. Neutrophils play a crucial role in inflammatory response against bacterial infections, once they are the first cells recruited to the sites of injury. In diabetes, there is a failure in the neutrophil functions, including migration, ROS production, phagocytosis, and bacterial killing, which are associated with the high incidence of bacterial infections. Herein, we point out pieces of evidence revealing the primary molecular mechanisms involved with impairment of neutrophil functions in diabetes, with relationship with high susceptibility to bacterial infections.

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Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases

Wang,

Jin,

Huang

et al. 2024

Drug Development Research

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Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil‐hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.

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Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes

Abstract: Neutrophil numbers and migration abilities displayed distinct levels in different types of diabetes. In T1D, CD62L seems to play an important role in the migration of neutrophils and β-cell autoimmunity.

Cited by 53 publications

References 36 publications

Abnormal Peripheral Neutrophil Transcriptome in Newly Diagnosed Type 2 Diabetes Patients

Abnormal Peripheral Neutrophil Transcriptome in Newly Diagnosed Type 2 Diabetes Patients

Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes

Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases

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