Abstract
Dendritic cell (DC) migration to secondary lymphoid organs is a crucial step to initiate adaptive immune responses. This step requires the expression of a functional CCR7 chemokine receptor on DC undergoing maturation. Here, we show that the natural retinoid 9-cis retinoic acid (9cRA) and the synthetic retinoid fenretinide (4-HPR) specifically inhibit the functional up-regulation of CCR7 on maturing human DCs, without affecting early steps of DC maturation. As a consequence, mature DCs do not migrate in vitro toward the chemokine CCL19. Importantly, 4-HPR and 9cRA by inhibiting the expression of CCR7 on bone marrow-derived murine DCs dampen their in vivo migration to draining lymph nodes. 4-HPR also inhibits the expression of the chemokine receptors CXCR4, therefore, impairing in vitro migration of human DCs to CXCL12 and inhibiting in vivo the CXCR4-dependent migration of the posterior lateral line primordium (PLLp) in zebrafish embryos. Taken together, these data highlight a novel function of retinoids and suggest the possibility of using retinoids to treat inflammatory or autoimmune diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alitretinoin
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Animals
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Bone Marrow / drug effects
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Bone Marrow / metabolism
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Cell Movement / drug effects*
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Cell Survival / drug effects
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Cells, Cultured
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Chemokine CXCL12 / metabolism
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Chemotaxis
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Dendritic Cells / drug effects*
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Dendritic Cells / metabolism
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Embryo, Nonmammalian / cytology
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Embryo, Nonmammalian / drug effects*
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Embryo, Nonmammalian / metabolism
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Enzyme-Linked Immunosorbent Assay
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Fenretinide / pharmacology*
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Flow Cytometry
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Gene Expression Regulation, Developmental
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Humans
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In Situ Hybridization
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In Vitro Techniques
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Interleukin-6 / metabolism
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Lymph Nodes / drug effects
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Mice
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Mice, Inbred C57BL
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, CCR7 / physiology*
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Receptors, CXCR4 / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Tretinoin / pharmacology*
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Zebrafish / physiology
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Zebrafish Proteins / physiology*
Substances
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Ccr7 protein, zebrafish
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Chemokine CXCL12
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Interleukin-6
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RNA, Messenger
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Receptors, CCR7
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Receptors, CXCR4
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Zebrafish Proteins
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Fenretinide
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Alitretinoin
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Tretinoin