IL-2 phosphorylates STAT5 to drive IFN-γ production and activation of human dendritic cells.
Human dendritic cells (hDCs) produce IL-2 and express IL-2R α-chain (CD25), but the role of IL-2 in DC functions is not well defined. A recent study suggested that the main function of CD25 on hDCs was to transpresent IL-2 to activate T lymphocytes. Our results demonstrate the expression of the three chains of the IL-2R on hDCs and that IL-2 induces STAT5 phosphorylation. Interestingly, use of inhibitors of p-STAT5 revealed that IL-2 increases LPS-induced IFN-γ through STAT5 phosphorylation. Finally, we report that IL-2 increases the ability of hDCs to activate helpless CD8(+) T cells, most likely because of IL-2-triggered IFN-γ synthesis, as we previously described. For the first time, to our knowledge, we disclose that IL-2 induces monocyte-derived hDC's functional maturation and activation through IL-2R binding. Interestingly, our study suggests a direct effect of anti-CD25 mAbs on hDCs that may contribute to their clinical efficacy.
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France; herr.florence@gmail.com.
Florence
F
Herr
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France;
Roxane
R
Lemoine
Unité Mixte de Recherche 7292, Centre National de la Recherche Scientifique, 37032 Tours, France; and.
Fabrice
F
Gouilleux
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France;
Daniel
D
Meley
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France;
Ihab
I
Kazma
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France;
Audrey
A
Heraud
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France;
Florence
F
Velge-Roussel
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France; Service de Néphrologie et d'Immunologie Clinique, Centre Hospitalier Régional Universitaire de Tours, 37044 Tours, France.
Christophe
C
Baron
L'Équipe d'Accueil 4245, Université François Rabelais, 37032 Tours, France; Service de Néphrologie et d'Immunologie Clinique, Centre Hospitalier Régional Universitaire de Tours, 37044 Tours, France.
Yvon
Y
Lebranchu
D000906:Antibodies / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology*
D000906:Antibodies; C573415:IFNG protein, human; C508594:IL2 protein, human; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides; D050799:STAT5 Transcription Factor; D007371:Interferon-gamma