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Blimp-1 inhibits Th9 cell differentiation and attenuates diabetic coronary heart disease
Haiyan Chen1, Fangyuan Gao2, Yi Bao1
1Department of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Insights
B lymphocyte-induced maturation protein 1 (Blimp-1) protects against diabetic coronary heart disease (DM-CHD) by inhibiting Th9 cell differentiation. Lower Blimp-1 levels correlate with increased Th9 cells and IL-9 in DM-CHD patients.
Area of Science:
- Immunology
- Cardiovascular Disease
- Endocrinology
Background:
- Diabetic coronary heart disease (DM-CHD) is a significant global health concern.
- Th9 cells and interleukin-9 (IL-9) are implicated in diabetes and atherosclerosis.
- The role of B lymphocyte-induced maturation protein 1 (Blimp-1) in DM-CHD pathogenesis is unknown.
Purpose of the Study:
- To investigate the role of Blimp-1 in DM-CHD.
- To determine if Blimp-1 regulates Th9 cell differentiation in DM-CHD.
Main Methods:
- Analysis of serum Blimp-1 mRNA, Th9 cell proportion (IL-9+ CD4+ T cells), and IL-9 levels in DM-CHD patients.
- Correlation analysis between Blimp-1 and IL-9 levels.
- Administration of Blimp-1-expressing lentiviruses (LV-Blimp-1) in DM-CHD model rats.
Main Results:
- DM-CHD patients showed decreased serum Blimp-1 mRNA and increased Th9 cells and IL-9.
- Serum Blimp-1 mRNA levels negatively correlated with IL-9 levels.
- LV-Blimp-1 treatment inhibited Th9 differentiation and reduced atherosclerotic lesions, dyslipidemia, inflammation, vascular dysfunction, and oxidative stress in rats.
Conclusions:
- Blimp-1 exerts a protective effect in diabetic coronary heart disease.
- Blimp-1 may exert its protective effects by inhibiting Th9 cell differentiation.
Abstract:
Diabetic coronary heart disease (DM-CHD) poses a major threat to the world. The newly described T cell subset-Th9 cells and related cytokine interleukin (IL)-9 play important roles in the pathogenesis of diabetes and atherosclerosis. B lymphocyte-induced maturation protein 1 (Blimp-1) has been indicated to negatively regulate Th9 development in allergic asthma, but its role in DM-CHD remains unclear. Hence, this study was designed to investigate the role of Blimp-1 in DM-CHD and to elucidate whether the mechanism was associated with regulation of Th9 cell differentiation. Our results showed that serum Blimp-1 mRNA level was decreased whereas proportion of Th9 cells (IL-9+ CD4+ T cells) and serum level of Th9-related IL-9 were increased in DM-CHD patients. Furthermore, serum Blimp-1 mRNA level was negatively correlated with IL-9 level in DM-CHD patients. Importantly, administration of lentiviruses expressing Blimp-1 (LV-Blimp-1) significantly inhibited Th9 cell differentiation and alleviated the severity of atherosclerotic lesions in the aorta and coronary artery, dyslipidemia, inflammation, vascular endothelial dysfunction, and oxidative stress in DM-CHD model rats. Collectively, Blimp-1 exerts a protective effect in DM-CHD rats and the mechanism might involve inhibition of Th9 cell differentiation.

