Dendritic cell phenotype and function are modulated by inflammation and insulin-resistance.

Objectives: Inflammation is involved vascular remodeling. Dendritic cells (DCs) are antigen presenting cells which may localize in the healthy human arterial wall and increase in the atherosclerotic lesion. Obesity and insulin resistance are well known risk factors for cardiovascular disease, and diabetic patients with atherosclerotic disease have compromised immune functions. We have previously reported that myeloid precursors of DCs isolated from obese and diabetic patients (obese T2D) show quantitative abnormalities and significantly increase their adhesiveness to vascular coronary smooth muscle cells. We then further in vitro characterized DC obtained in vitro from obese T2D patients. Materials and methods: DCs were obtained from circulating PBMC of obese and obese T2D patients and characterized by flow cytometry. Expression of integrins mRNAs was assessed by Real time PCR. Activation and proliferation of lymphocytes was performed by CFSE assay. Results: Real time PCR demonstrated that DCs from obese T2D patients significantly increased the expression of CD18, CD11c and DC-SIGN, while no differences were found in obese patients compared to control subjects. CFSE analysis demonstrated that T2D DCs were less able to stimulate lymphocyte proliferation, in line with the phenotypical characterization, compared to control subjects. No morphological differences were found between T2D DCs and healthy controls, by means of electron microscopy. Conclusion: Inflammation and insulin-resistance affect DC phenotype and function. Therefore DCs may be candidate to a major role in the onset and progression of vascular inflammation and remodeling, suggesting that they could be a target for therapy