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

J Leukoc Biol. 2008 Sep;84(3):871-9. doi: 10.1189/jlb.0108047. Epub 2008 May 30.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alitretinoin
  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism
  • Chemotaxis
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fenretinide / pharmacology*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Humans
  • In Situ Hybridization
  • In Vitro Techniques
  • Interleukin-6 / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR7 / physiology*
  • Receptors, CXCR4 / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tretinoin / pharmacology*
  • Zebrafish / physiology
  • Zebrafish Proteins / physiology*


  • Ccr7 protein, zebrafish
  • Chemokine CXCL12
  • Interleukin-6
  • RNA, Messenger
  • Receptors, CCR7
  • Receptors, CXCR4
  • Zebrafish Proteins
  • Fenretinide
  • Alitretinoin
  • Tretinoin