Abstract
Inflammatory monocyte-derived dendritic cells (Mo-DCs) have been described in several chronic inflammatory disorders, such as rheumatoid arthritis (RA), and are suspected to play a detrimental role by fueling inflammation and skewing adaptive immune responses. However, the characterization of their phenotype is still limited, as well as the comprehension of the factors that govern their differentiation. Here, we show that inflammatory Mo-DCs generated in vitro expressed a large and atypical panel of C-type lectin receptors, including isoforms of CD209 and CD206, CD303 and CD207, as well as intracellular proteins at their surfaces such as the lysosomal protein CD208. Combination of these markers allowed us to identify cells in the synovial fluid of RA patients with a close phenotype of inflammatory Mo-DCs generated in vitro. Finally, we found in coculture experiments that RA synoviocytes critically affected the phenotypic differentiation of monocytes into Mo-DCs, suggesting that the crosstalk between infiltrating monocytes and local mesenchymal cells is decisive for Mo-DCs generation.
Keywords:
C-type lectin receptors; DC-LAMP; Toll-like receptors; dendritic cells; rheumatoid arthritis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / genetics
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Antigens, CD / immunology
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Arthritis, Rheumatoid / genetics
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / pathology
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B7 Antigens / genetics
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B7 Antigens / immunology
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / immunology
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Cell Differentiation
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Coculture Techniques
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Dendritic Cells / immunology*
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Dendritic Cells / pathology
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Gene Expression Regulation / immunology*
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Humans
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Immunophenotyping
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Lysosomal Membrane Proteins / genetics
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Lysosomal Membrane Proteins / immunology
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Mannose-Binding Lectins / genetics
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Mannose-Binding Lectins / immunology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Monocytes / immunology*
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Monocytes / pathology
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology
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Phenotype
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Interleukin / genetics
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Receptors, Interleukin / immunology
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Signal Transduction
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Synovial Fluid / cytology
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Synovial Fluid / immunology
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Synoviocytes / immunology*
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Synoviocytes / pathology
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Toll-Like Receptors / genetics
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Toll-Like Receptors / immunology
Substances
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Antigens, CD
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B7 Antigens
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CD207 protein, human
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CLEC4C protein, human
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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LAMP3 protein, human
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Lectins, C-Type
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Lysosomal Membrane Proteins
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MRC1 protein, human
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Mannose-Binding Lectins
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Membrane Glycoproteins
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Neoplasm Proteins
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Interleukin
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Toll-Like Receptors