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Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon

Abstract

We have identified two cell subsets in human blood based on the lack of lineage markers (lin) and the differential expression of immunoglobulin-like transcript receptor 1 (ILT1) and ILT3. One subset (lin/ILT3+/ILT1+) is related to myeloid dendritic cells. The other subset (lin/ILT3+/ILT1) corresponds to 'plasmacytoid monocytes'. These cells are found in inflamed lymph nodes in and around the high endothelial venules. They express CD62L and CXCR3, and produce extremely large amounts of type I interferon after stimulation with influenza virus or CD40L. These results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon. Plasmacytoid monocytes may protect other cells from viral infections and promote survival of antigen-activated T cells.

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Figure 1: Differential expression of ILT1 and ILT3 allows the identification of two distinct subsets of primary dendritic cell precursors in human peripheral blood.
Figure 2: Morphology of ILT3+/1+ and ILT3+/1 cells.
Figure 3: Phenotype of PMs and interdigitating dendritic cells in mycobacteria-infected lymph nodes and of germinal center dendritic cells in inflamed tonsils.
Figure 4: CD62L expression.
Figure 5: ILT3+/1 cells produce large amounts of type I IFN after being stimulated with influenza virus and CD40L.
Figure 6: T cell-polarizing and -stimulating capacities of ILT3+/1 and ILT3+/1+ cells, and monocyte-derived dendritic cells.

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Acknowledgements

We thank M. Dessing and A. Pickert (Basel Institute for Immunology) for assistance in cell sorting; F. Montero (Immunotech, Marseille) for IL-5Rα antibody; P. Lane (Birmingham Medical School, Birmingham, UK) and A. Vitiello (R.W. Johnson Pharmaceutical Research Institute, San Diego, California) for reagents; S. Gilfillan, H.-R. Rodewald, A. Rolink and F. Sallusto (Basel Institute for Immunology) for reviewing the manuscript. The Basel Institute for Immunology was founded and is supported by Hoffmann-La Roche, CH-4002 Basel.

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Correspondence to Marco Colonna.

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Cella, M., Jarrossay, D., Facchetti, F. et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 5, 919–923 (1999). https://doi.org/10.1038/11360

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