Monocytic HLA-DR expression in type 2 diabetes mellitus: Impact on disease susceptibility

Abstract

Monocytes are innate immune cells that act as antigen-presenting cells. HLA-DR is a cell surface protein that plays a crucial role in the immune system by presenting antigens to CD4 T Cells (T helper). Based on surface expression, monocytes can differentiate into three subsets; classical monocytes (CD14+CD16-), intermediates monocytes (CD14+ CD16+), and non-classical monocytes (CD14dim CD16+). Among these subsets, classical monocytes have the lowest, and intermediate monocytes have the highest expression of HLA-DR. Monocytes are very sensitive to environmental changes, like hyperglycemia in Type 2 Diabetes Mellitus (T2DM). Metabolic changes in T2DM conditions trigger changes in immune cells including monocytes. Chronic low-grade inflammation in T2DM decreased HLA-DR expression in all monocyte subsets. Monocytes that do not express or lose HLA-DR expression are known as CD14+HLA-DR-/low monocyte and is immunosuppressive. This increase in monocytes in T2DM conditions is related to the ability of monocytes as antigen-presenting cells. Decreased HLA-DR expression increased the risk of severity and susceptibility to several diseases such as COVID-19 infection, TB, cancer, or sepsis. The alterations in HLA-DR expression are one of the factors that make T2DM a comorbid disease. This literature review aims to explore monocytic HLA-DR in T2DM conditions hence increasing the risk of severity and susceptibility to disease. This literature is expected to be the basis for research on the potential of HLA-DR as a prevention or treatment for T2DM patients.