PUBLICATION

Selected natural and synthetic retinoids impair CCR7- and CXCR4-dependent cell migration in vitro and in vivo

Authors
Villablanca, E.J., Zhou, D., Valentinis, B., Negro, A., Raccosta, L., Mauri, L., Prinetti, A., Sonnino, S., Bordignon, C., Traversari, C., and Russo, V.
ID
ZDB-PUB-080610-8
Date
2008
Source
Journal of Leukocyte Biology   84(3): 871-879 (Journal)
Registered Authors
Keywords
dendritic cells, chemokine receptors, zebrafish
MeSH Terms
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/metabolism
  • Fenretinide/pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Zebrafish Proteins/physiology*
  • Cell Movement/drug effects*
  • Chemokine CXCL12/metabolism
  • Cell Survival/drug effects
  • Mice, Inbred C57BL
  • Zebrafish/physiology
  • Flow Cytometry
  • In Situ Hybridization
  • Humans
  • Chemotaxis
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Tretinoin/pharmacology*
  • Interleukin-6/metabolism
  • Dendritic Cells/drug effects*
  • Dendritic Cells/metabolism
  • In Vitro Techniques
  • Bone Marrow/drug effects
  • Bone Marrow/metabolism
  • Receptors, CCR7/physiology*
  • Animals
  • Reverse Transcriptase Polymerase Chain Reaction
  • Lymph Nodes/drug effects
  • Lymph Nodes/metabolism
  • Lymph Nodes/pathology
  • Receptors, CXCR4/physiology*
  • Mice
(all 34)
PubMed
18515328 Full text @ J. Leukoc. Biol.
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.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
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Orthology
Engineered Foreign Genes
Mapping
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Citation
Villablanca, E.J., Zhou, D., Valentinis, B., Negro, A., Raccosta, L., Mauri, L., Prinetti, A., Sonnino, S., Bordignon, C., Traversari, C., and Russo, V. (2008) Selected natural and synthetic retinoids impair CCR7- and CXCR4-dependent cell migration in vitro and in vivo. Journal of Leukocyte Biology. 84(3):871-879.