Retinoids regulate survival and antigen presentation by immature dendritic cells.
Maturation of dendritic cells (DCs) is a critical step for the induction of an immune response. We have examined the role of retinoid nuclear receptor pathways in this process. Retinoids induce DC apoptosis, in the absence of inflammatory signals, through retinoic acid receptor (RAR)alpha/retinoic X receptor (RXR) heterodimers. In contrast, via a cross talk with inflammatory cytokines, retinoids increase DNA binding activity of nuclear factor kappaB in DCs, trigger membrane major histocompatibility complex class II and costimulatory molecule expression, induce the differentiation of immature DCs into mature DCs, and enhance antigen-specific T cell response. This maturation of DCs is mediated via a RXR-dependent/RAR-independent pathway and via an RARalpha/RXR pathway distinct from the one responsible for apoptosis. Apoptosis and activation, mediated through distinct nuclear retinoid receptor pathways, can be dissociated from each other with selective synthetic retinoids. We identify a novel cellular function for retinoids and suggest that selective retinoids might be of interest for controlling antigen presentation.
Geissmann
Frédéric
F
UPRES EA 219 Service d'Anatomie Pathologique EA 219, Hopital Necker-Enfants Malades, 161 rue de Sevres, 75743 Paris Cedex 15, France. geissman@necker.fr
Revy
Patrick
P
Brousse
Nicole
N
Lepelletier
Yves
Y
Folli
Claudia
C
Durandy
Anne
A
Chambon
Pierre
P
Dy
Michel
M
D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000378:metabolism; D061945:Caspase Inhibitors; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D019281:Dimerization; D005802:Genes, MHC Class II; D006680:HLA Antigens; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D061945:Caspase Inhibitors; D004268:DNA-Binding Proteins; D006680:HLA Antigens; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand