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Published on: February 17, 2023
Insulin resistance and obesity affect monocyte-derived dendritic cell phenotype and function
Sara Paccosi1, Laura Pala2, Barbara Cresci2
1Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy.
Insights
Dysfunctional dendritic cells (DCs) in obese, post-menopausal women with type 2 diabetes (T2DM) may increase vascular inflammation. This dysfunction, linked to obesity and diabetes, impacts immune cells crucial for cardiovascular health.
Area of Science:
- Immunology
- Endocrinology
- Cardiovascular Science
Background:
- Cardiovascular disease (CVD) is common in post-menopausal women, linked to obesity and insulin resistance.
- Immunological mechanisms, particularly dendritic cells (DCs), play a role in vascular remodeling, but their specific function in this context is unclear.
Purpose of the Study:
- To characterize monocyte-derived dendritic cells (Mo-DCs) in post-menopausal women with type 2 diabetes (T2DM) and obesity.
- To investigate Mo-DC function and phenotype in relation to atherosclerosis risk factors.
Main Methods:
- Phenotypic and functional characterization of Mo-DCs using flow cytometry and mixed lymphocyte reactions.
- Assessment of mRNA integrin expression and circulating fetuin-A and adiponectin levels.
Main Results:
- Mo-DCs showed phenotypic dysregulation, defective lymphocyte stimulation, and increased mRNA for adhesion molecules (CD11c, CD18, DC-SIGN/CD209).
- Altered fetuin-A and adiponectin levels were observed, negatively correlated with each other.
- Hyperglycemia impaired the conversion of CD14+ cells into Mo-DCs.
Conclusions:
- Mo-DCs are dysfunctional in obese, post-menopausal women with T2DM, even without clinical CVD.
- The combination of obesity and diabetes exacerbates Mo-DC dysfunction, potentially increasing vascular inflammation.
Aim:
Cardiovascular disease (CVD) is prevalent in women after menopause, which may be associated with obesity, insulin resistance and metaflammation. Despite the recognized role of immunological mechanisms in vascular remodeling, the role of dendritic cells (DCs) is still unclear. The aim was to characterize monocyte-derived DCs (Mo-DC) in post-menopausal patients with type 2 diabetes (T2DM) and obese woman, without clinical manifestations of atherosclerosis.
Methods:
Obese post-menopausal women with or without T2DM were enrolled and were compared to age-matched healthy women. DCs obtained from patients were phenotypically and functionally characterized by flow cytometry and mixed lymphocyte reaction. MRNA integrins expression was assessed by real time RT-PCR; circulating fetuin-A and adiponectin levels were measured by ELISA.
Results:
Phenotypic dysregulation of Mo-DC reported was related to a defective allogenic lymphocyte stimulation and to an increased mRNA of CD11c, CD18 and DC-SIGN/CD209 which regulate their adhesion to vascular wall cells. Fetuin-A and adiponectin levels were significantly altered and negatively correlated. Hyperglycaemia significantly impaired CD14+ transdifferentiation into Mo-DC.
Conclusions:
These data show a dysfunction of Mo-DCs obtained from precursors isolated from T2DM obese post-menopausal woman without any documented clinical CV event. Association of obesity to diabetes seems to worsen DC's phenotype and function and increase vascular inflammation.
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