Eosinophils from patients with type 1 diabetes mellitus express high level of myeloid alpha-defensins and myeloperoxidase

Neuwirth, Aleš; Dobeš, Jan; Oujezdská, Jana; Ballek, Ondřej; Benešová, Martina; Šumnı́k, Zdenĕk; Včeláková, Jana; Koloušková, Stanislava; Obermannová, Barbora; Kolář, Michal; Stechova, Katerina; Filipp, Dominik

doi:10.1016/j.cellimm.2011.12.001

Cited by 25 publications

(15 citation statements)

References 25 publications

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“…The majority of the identified genes were associated with the cytotoxicity or activation of neutrophils. These include α‐defensins ( DEFA1, DEFA1B, DEFA3, DEFA4 ) 28‐30 and the neutrophil azurophilic granule proteins cathepsin G ( CTSG ), elastase ( ELANE ), myeloperoxidase ( MPO ), bactericidal/permeability‐increasing protein ( BPI ) and azurocidin 1 ( AZU1 ). CEACAM6 (CD66c) and CEACAM8 (CD66b) are also known to activate neutrophils and eosinophils 31‐33 …”

Section: Resultsmentioning

confidence: 99%

“…We also found 19 genes (in cluster 8) were higher in non‐responders than responders before and after omalizumab treatment (Figure 3A). They, including genes encoding defensins 29,30,66 elastase 67 CD66b, 33 were highly associated with neutrophil and eosinophil activation and cytotoxicity (Figure 3B). In addition, neutrophil signatures were relatively well maintained in both groups even with omalizumab treatment and this was not due to a discrepancy in cell counts.…”

Section: Discussionmentioning

confidence: 99%

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Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab

Upchurch

Wiest

Cardenas

et al. 2020

Clin Experimental Allergy

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Background Anti‐IgE (omalizumab) has been used for the treatment of moderate‐to‐severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with significant clinical benefits. Objective To investigate the transcriptional variations between omalizumab responders and non‐responders and to study the mechanisms of action of omalizumab. Methods The whole blood transcriptomes of moderate‐to‐severe adult asthma patients (N = 45:34 responders and 11 non‐responders) were analysed over the course of omalizumab treatment. Non‐asthmatic healthy controls (N = 17) were used as controls. Results Transcriptome variations between responders and non‐responders were identified using the genes significant (FDR < 0.05) in at least one comparison of each patient response status and time point compared with control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non‐responders tend to remain more similar to their pre‐treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were up‐regulated in non‐responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non‐responders. Conclusion and Clinical Relevance This study provides not only transcriptional variations between omalizumab responders and non‐responders, but also molecular insights for controlling asthma by omalizumab.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab

Upchurch

Wiest

Cardenas

et al. 2020

Clin Experimental Allergy

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“…Eosinophils were also found to associate with insulin resistance and β‐cell dysfunction in prediabetic subjects, as well as corticoadrenal insufficiency . Eosinophils are linked to the development of type I diabetes and express high levels of myeloid alpha‐defensins and myeloperoxidase in patients with Type 1 diabetes mellitus . Remarkably, eosinophils express multiple hormone receptors, implicating that their activity in peripheral tissues may be subject to systemic‐level regulation by the endocrine system.…”

Section: Tissue Ligands Regulatory For Eosinophil Accumulation Phenomentioning

confidence: 99%

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Abdala‐Valencia

Coden

Chiarella

et al. 2018

Journal of Leukocyte Biology

114

109

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Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial-mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.

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“…In accordance with this, Neuwrith et al . have reported a role of CD15 low cells in T1D development . Alterations in the frequency of CD16 monocytes has been associated with diabetes complications .…”

Section: Introductionmentioning

confidence: 99%

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

Singh

Martinell

Luo

et al. 2019

Clinical and Experimental Immunology

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Summary There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age‐matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)‐35 were measured by enzyme‐linked immunosorbent assay (ELISA). The proportion of CD11c+CD123– antigen‐presenting cells (APCs) was lower, while the proportions of CD11c+CD123+ APCs and IL‐35+ tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3–CD56highCD16+ natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL‐35+ regulatory T cells and plasma IL‐35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL‐35+ regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

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Eosinophils from patients with type 1 diabetes mellitus express high level of myeloid alpha-defensins and myeloperoxidase

Cited by 25 publications

References 25 publications

Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab

Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

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