Blimp-1 inhibits Th9 cell differentiation and attenuates diabetic coronary heart disease

Int Immunopharmacol. 2021 Jun:95:107510. doi: 10.1016/j.intimp.2021.107510. Epub 2021 Mar 8.

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.

Keywords: Atherosclerosis; Blimp-1; Diabetic coronary heart disease; IL-9; Th9.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Differentiation
  • Coronary Disease / immunology*
  • Diabetes Mellitus, Type 2 / immunology*
  • Female
  • Humans
  • Interleukin-9 / immunology
  • Male
  • Middle Aged
  • Positive Regulatory Domain I-Binding Factor 1 / genetics
  • Positive Regulatory Domain I-Binding Factor 1 / immunology*
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocyte Subsets / immunology*

Substances

  • Interleukin-9
  • Positive Regulatory Domain I-Binding Factor 1