Elevated levels of peripheral blood <scp>CD</scp>14bright<scp>CD</scp>16+ and <scp>CD</scp>14dim<scp>CD</scp>16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes

Ryba-Stanisławowska, Monika; Myśliwska, Jolanta; Juhas, Ulana; Myśliwiec, Małgorzata

doi:10.1111/apm.12419

Cited by 12 publications

(12 citation statements)

References 24 publications

(37 reference statements)

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“…This causes change in a profile of released cytokines upon receptor activation [ 43 ]. Based on our results and literature [ 5 , 44 , 45 ] it is highly probable that CD16 + monocytes play an important role in promoting inflammatory response in DM1.…”

Section: Discussionsupporting

confidence: 65%

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus

et al. 2017

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The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-α gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 −397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The analysis concerned PvuII polymorphism of the ER-α gene as well as the levels of serum inflammatory markers (CRP, IL-6, TNF-α), proangiogenic factors (VEGF, angiogenin), 17β-estradiol, values of monocyte subsets (CD14++CD16− and CD14+CD16+), lipid profile, and blood pressure. In our study, girls with CC genotype had lower level of inflammatory and angiogenic factors and lower frequencies of CD14+CD16+ monocytes in comparison to CT or TT carriers. Simultaneously, the CC carriers had a greater population of CD14++CD16− monocytes, increased blood pressure, and serum levels of: estrogen, total cholesterol, triglycerides, and low-density lipoprotein cholesterol than girls bearing CT or TT genotype. Our study suggests a pleiotropic effect of PvuII polymorphic CC variant on diabetic vasculopathies. Although the CC genotype carriers demonstrate less inflammatory and angiogenic activity, they seem to display less favorable cardiometabolic features. Based on our study, we cannot distinguish PvuII ER-α genotype that could be useful in identification of DM1 girls that are more prone to develop of late vascular complications, before the occurrence of first clinical symptoms.

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Section: Discussionsupporting

confidence: 65%

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus

et al. 2017

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“…Diabetic macrophages are hyperresponsive to inflammatory stimuli in vitro, are less able to switch to alternatively activated phenotypes, and exhibit a prolonged inflammatory phenotype in diabetic wounds (4,11,29). There is also evidence for diabetes altering the number or phenotype of nonlassical monocytes in humans (30)(31)(32). Together with diabetes-induced changes in other myeloid cell lineages such as neutrophils (7), macrophages drive the elevated, nonresolving inflammatory state of chronic nonhealing diabetic wounds (33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

Cx3CR1 Expression Identifies Distinct Macrophage Populations That Contribute Differentially to Inflammation and Repair

et al. 2019

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Bone marrow (BM)-derived classical monocytes are critical to wound repair, where they differentiate into macrophages and purge foreign materials and dead cells while also laying the framework for tissue repair and regeneration. A subset of this recruited population persists in the wound and acquires alternative activation states to promote cell proliferation and matrix remodeling. In diabetes, this phenotypic switch is impaired and inflammation persists in an elevated state, contributing to delayed wound healing. Long-term tissue-resident macrophages can also play a key role in the resolution of inflammation to varying degrees across different organs. In this study, we investigated different macrophage subpopulations in nondiabetic and diabetic wounds over time using Cx3CR1 eGFP transgenic mice and BM transplants. We show Cx3CR1 eGFP-hi macrophages in skin wounds are derived from long-term tissue-resident macrophages and predominantly exhibit an alternative activation state, whereas cells expressing low-intermediate Cx3CR1 eGFP are derived from the BM, contribute to both early and later stages of wound healing, and show both classical and alternative activation states. Diabetic mice showed significant differences in the dynamics of these subpopulations, which likely contribute to elevated and persisting inflammatory states over time. In particular, failure of Cx3CR1 int macrophages to mature into Cx3CR1 hi links maturation to resolution of inflammation. Thus strategies to promote macrophage maturation may be effective therapeutic tools in chronic inflammatory environments. ImmunoHorizons, 2019, 3: 262-273.

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“…Enhanced monocyte activity, phenotype changes [9,10] and their ability to spontaneous production of pro-inflammatory cytokines [11] were recently reported in type 1 diabetes. In our previous works, we observed an increased number of non-classical and intermediate monocytes in peripheral blood of complication-free DM1 juvenile patients [12,13]. Others showed that DM1 subjects with late diabetic complications are characterised by a lower frequency of blood CD16 + cells in comparison with complication-free ones.…”

Section: Introductionmentioning

confidence: 63%

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

et al. 2019

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Alternatively activated macrophages (M2) exert anti-inflammatory effects and are crucial for keeping balance between protective and destructive cell-mediated immunity in healing phase of inflammation. Two members of the interferon regulatory factors family, IRF5 and IRF4, are known to promote M1 or M2 phenotype, respectively. Our study aimed to analyse the effectiveness of the M2 differentiation process in vitro (achieved by IL-4 stimulation) and its relationship to the stage of type 1 diabetes mellitus (DM1) in juvenile patients. To identify the basic changes in M2 phenotype, we examined the expression of the surface CD206, CD14, CD86 molecules, intracellular IRF4 and IRF5 transcription factors as well as IL-10 and TNFα intracellular production. Ten newly diagnosed (ND-DM1) and ten long-standing (LS-DM1) patients were enrolled into the study. The control group consisted of six children. We observed a significantly higher number of unpolarised CD206 + CD14 + cells in the M2 cultures of DM1 subjects when compared to healthy ones. Examined cells presented common features with M1 macrophages (high levels of the CD14/CD86/IRF5 markers); however, they were weak TNFα producers in ND-DM1 patients. For the first time, we have revealed dysregulated IRF4/IRF5 axis in the analysed subpopulation derived from diabetic patients. Additionally, monocytes of ND-DM1 children were still able to differentiate into regulatory IL-10 + M2 macrophages, while this process was highly limited in LS-DM1 patients. Summarising, we suggest that the M2 polarisation process is less effective in DM1 patients than in healthy subjects and it may vary depending on the stage of disease. It can be concluded that in vitro differentiated M2 macrophages may be used in the future as inflammatory inhibitors for adoptive therapy experiments in ND-DM1 subjects.

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Elevated levels of peripheral blood CD14^brightCD16⁺ and CD14^dimCD16⁺ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes

Cited by 12 publications

References 24 publications

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus

Cx3CR1 Expression Identifies Distinct Macrophage Populations That Contribute Differentially to Inflammation and Repair

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

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Elevated levels of peripheral blood CD14brightCD16+ and CD14dimCD16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes

Cited by 12 publications

References 24 publications

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus

Cx3CR1 Expression Identifies Distinct Macrophage Populations That Contribute Differentially to Inflammation and Repair

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

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Elevated levels of peripheral blood CD14^brightCD16⁺ and CD14^dimCD16⁺ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes