Deciphering the molecular changes of MDP- and GMP-derived monocytes in response to M-CSF and GM-CSF stimulation
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Monocytes account for 10% of our total blood leucocytes and play an important role in our innate immune defense. They form a heterogenous group of cells and arise from separate progenitors, namely monocyte-dendritic cell progenitors (MDPs), and granulocyte-monocyte progenitors (GMPs). The ontogenies as well as environmental cues like cytokines influence the fate and function of these monocytes. However, the differential response of MDP- and GMP-derived monocytes to the cytokines, macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the phenotypic changes as a result of cytokine encounter remains poorly understood. Hence, in this study, we employed transgenic mice models, in vitro cell cultures, cell imaging, cell sorting, and flow cytometry to investigate the response of MDP- and GMP-derived monocytes to M-CSF and GM-CSF stimulation. Overall, our results demonstrate that classical monocytes (CMs) derived from MDPs and GMPs have a distinct cell surface expression with discrete major histocompatibility class II (MHCII) pattern under M-CSF and GM-CSF treatment. M-CSF induces a homeostatic profile with a macrophage-like phenotype. GM-CSF, on the other hand, drives a dendritic cell-like phenotype with high MHCII expression. Although very low, GM-CSF also promoted expression of CD319 (a marker for MDP-derived CMs) in MHCIIhigh GMP-derived CMs. Collectively, we provide an insight into how environmental factors shape the heterogeneity and expression of CMs that can be studied in various disease contexts. Moreover, these results can advance our understanding of the fluctuations seen in specific monocyte subsets under inflammatory conditions and how different cytokines play a role in promoting their pathogenic function.