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Impaired efferocytosis by monocytes and monocyte-derived macrophages in patients with poorly controlled type 2
Qian-Yun Mao1, Hui Ran1, Qiu-Yue Hu1
1Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Background:
Deficient efferocytosis (i.e., phagocytic clearance of apoptotic cells) by macrophages has been frequently reported in experimental models of type 2 diabetes (T2D).
Aim:
To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.
Methods:
Overall, 30 patients with poorly controlled T2D [glycosylated hemoglobin (HbA1c) ≥ 8.0%] and 30 age- and sex-matched control subjects were enrolled in the study. The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining. Macrophage membrane CD14 expression was examined by flow cytometry. Metabolic factors such as 25(OH)D and immune factors such as interleukin-1β were also measured.
Results:
The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group. Notably, efferocytosis remained impaired after monocytes differentiated into macrophages. Additionally, the percentages of classical monocytes (CD14++CD16- monocytes) and CD14+ macrophages were significantly lower in the diabetes group. Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level, and that the macrophage efferocytosis index was significantly associated with the percentage of CD14+ macrophages.
Conclusion:
Impaired efferocytosis was observed in T2D patients, with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages. The efferocytosis index was negatively associated with metrics of glycemic control, and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.
Insights
Impaired efferocytosis, the clearance of apoptotic cells, is evident in type 2 diabetes (T2D) patients. Poor glycemic control negatively impacts this crucial immune function in both monocytes and macrophages.
Area of Science:
- Immunology
- Metabolic Diseases
- Cell Biology
Background:
- Deficient efferocytosis (phagocytic clearance of apoptotic cells) is a known issue in experimental type 2 diabetes (T2D).
- Translating these findings to human patients is crucial for understanding T2D pathophysiology.
Purpose of the Study:
- To investigate whether efferocytosis capacity is impaired in blood monocytes and monocyte-derived macrophages of T2D patients.
- To correlate efferocytosis capacity with glycemic control and CD14 expression.
Main Methods:
- Assessed efferocytosis in 30 T2D patients and 30 controls using flow cytometry and immunostaining.
- Measured CD14 expression on macrophages and assessed metabolic/immune factors.
- Utilized multivariate linear regression to analyze associations.
Main Results:
- T2D patients exhibited significantly lower monocyte and macrophage efferocytosis indices compared to controls.
- Efferocytosis remained impaired in macrophages derived from T2D monocytes.
- Monocyte efferocytosis index correlated with HbA1c, and macrophage efferocytosis index correlated with CD14+ macrophage percentage.
Conclusions:
- Type 2 diabetes impairs efferocytosis in both monocytes and macrophages.
- Poor glycemic control (high HbA1c) is linked to reduced efferocytosis.
- Glucotoxicity may reduce efferocytosis by decreasing CD14 expression.
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