Clinical significance of monocyte heterogeneity

Abstract

Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.

Keywords: Atherosclerosis; Autoimmune Disease; CD14; CD16; Cardiovascular; Human; Ly6C; Macrophage; Monocyte; Mouse.

Figure 1

Sample gating strategy showing three human monocyte populations based on expression of CD14 and CD16. Relative expression of CD14 (x-axis) and CD16 (y-axis) is demonstrated on log scale. Classical monocytes (CD14⁺⁺CD16⁻) are gated in the green box, intermediate monocytes (CD14⁺⁺CD16⁺) in the red box, and non-classical monocytes (CD14⁺CD16⁺⁺) in the lavender box.