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IL-6 switches the differentiation of monocytes from dendritic cells to macrophages

Abstract

Monocytes can give rise to either antigen presenting dendritic cells (DCs) or scavenging macrophages. This differentiation is initiated when monocytes cross the endothelium. But the regulation of DC and macrophage differentiation in tissues remains elusive. When stimulated with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), monocytes yield DCs. However, we show here that the addition of fibroblasts switches differentiation to macrophages. On contact with monocytes, fibroblasts release IL-6, which up-regulates the expression of functional M-CSF receptors on monocytes. This allows the monocytes to consume their autocrine M-CSF. Thus, the interplay between IL-6 and M-CSF switches monocyte differentiation to macrophages rather than DCs, and IL-6 is an essential factor in the molecular control of antigen presenting cell development.

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Figure 1: Fibroblasts skew monocyte differentiation to macrophages.
Figure 2: The CD1a and CD14 flow cytometry profile. Table 1. Cytokine concentrations at day 5 for each culture condition.
Figure 3: Fibroblasts skew the differentiation of monocytes to macrophages through IL-6.
Figure 4: IL-6 and M-CSF interplay during the switch of monocyte differentiation towards DCs or macrophages.
Figure 5: M-CSF triggers internalization of M-CSFR on IL-6–treated DCs.
Figure 6: Differentiation of monocytes into either macrophages or DCs.

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Acknowledgements

We thank E. Kraus and C. Dantin for technical help, and B. Pulendran and V. Pascual for reading the manuscript. Supported by grants from NIH CA-78846-01A1 and Baylor Health Care Systems Foundation.

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Correspondence to Jacques Banchereau or A. Karolina Palucka.

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Chomarat, P., Banchereau, J., Davoust, J. et al. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 1, 510–514 (2000). https://doi.org/10.1038/82763

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