Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients

Musilli, Claudia; Paccosi, Sara; Pala, Laura; Gerlini, Gianni; Ledda, F.; Alessandro, Mugelli; Rotella, Carlo Maria; Parenti, Astrid

doi:10.1016/j.molimm.2011.08.019

Cited by 37 publications

(29 citation statements)

References 23 publications

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“…These studies showed that if depletion of CD11c + macrophages or inhibition of macrophage recruitment via MCP-1 knockout in obese mice could significantly reduce inflammation and increase insulin sensitivity (Kamei et al, 2006;Kanda et al, 2006;Patsouris et al, 2008). Increasing evidence in animals and humans about inflammation-induced insulin resistance in T2D were provided, and included abnormalities of lymphocytes (DeFuria et al, 2013;Winer et al, 2011), neutrophils (Talukdar et al, 2012), eosinophils , mast cells (Liu et al, 2009) and dendritic cells (Musilli et al, 2011). Therefore, the biggest challenge for treatment of T2D was modifying these immune cells to repair the insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Pham

et al. 2016

Biomed Res Ther

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Introduction: Type 2 diabetes mellitus (T2D) is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, although T2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC) transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype.All patients were transfused with ADSCs at 1-2x10 6 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months). Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46), there was no contamination of mycoplasma, and endotoxin levels were low (<0.25 EU/mL). No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.

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Section: Discussionmentioning

confidence: 99%

Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Pham

et al. 2016

Biomed Res Ther

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“…A recent study reported increased plasma levels of GM-CSF in T2D patients, which correlated with an activated state of myeloid and plasmocytoid DCs [33]. Moreover, in conditions of insulin-resistance and obesity an up-regulation of myeloid DCs was reported, which might contribute to pathological vascular remodeling [34]. As such, increased levels of GM-CSF in prediabetic subjects, together with the augmented TNF-α and IL-6 concentrations can place them at a higher risk for developing CVD.…”

Section: Discussionmentioning

confidence: 99%

Cytokine profiling of young overweight and obese female African American adults with prediabetes

et al. 2013

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Approximately 5–10% of subjects with prediabetes become diabetic every year. Inflammation is involved in the development of obesity-related type 2 diabetes (T2D). However, to date, the relationship between inflammation and prediabetes, defined by hemoglobin A1c (HbA1c) ≥ 5.7 and < 6.5%, remains largely unexplored, especially in African Americans. Therefore, in this study we examined a comprehensive panel of 13 cytokines involved in the inflammatory response in overweight/obese subjects with prediabetes. A total of 21 otherwise healthy, overweight/obese, young adult African American females with prediabetes, together with 20 matched overweight/obese controls, were selected for this study. Plasma cytokines were assessed by multiplex cytokine profiling. Plasma concentrations of interleukin (IL)-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) were significantly higher in the prediabetic group, as compared to the control group (all p < 0.05). Plasma concentrations of all the other cytokines, interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and IL-13, seemed to be elevated in the prediabetic group, but failed to reach statistical significances. Upon merging both groups, HbA1c was found to be positively correlated with IFN- γ, IL-1β, IL-2, IL-5, IL-7, IL-8, TNF-α and GM-CSF. This study demonstrates elevated levels of various pro-inflammatory cytokines in overweight/obese young subjects with prediabetes, which place them at higher risk of developing T2D and cardiovascular diseases. Our data also call for further investigations in animal models and population cohorts to establish the roles of a variety of pro-inflammatory cytokines in the early development of obesity-related T2D.

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“…The impact of obesity on myeloid DC number and function, [10][11][12] and associated viral responses, 13,14 has been described in several reports to date. The aim of this study was to further examine the effect of obesity on human DC function and T-cell instruction.…”

Section: Introductionmentioning

confidence: 99%

Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection

et al. 2013

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Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7 ± 7.3 kg m À 2 ), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.

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Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients

Cited by 37 publications

References 23 publications

Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Cytokine profiling of young overweight and obese female African American adults with prediabetes

Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection

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