Defective dendritic cell migration and activation of adaptive immunity in PI3Kγ-deficient mice

• Published in: The EMBO journal 2004-09, Vol.23 (17), p.3505-3515
• Main Authors: Del Prete, Annalisa, Vermi, William, Dander, Erica, Otero, Karel, Barberis, Laura, Luini, Walter, Bernasconi, Sergio, Sironi, Marina, Santoro, Amerigo, Garlanda, Cecilia, Facchetti, Fabio, Wymann, Matthias P, Vecchi, Annunciata, Hirsch, Emilio, Mantovani, Alberto, Sozzani, Silvano
• Format: Article
• Language: English
• Subjects: chemokines; chemotaxis; contact hypersensitivity; dendritic cells; EMBO19; EMBO37; PI3Kγ−/− mice
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600361

Gene‐targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3‐kinase (PI3Kγ) in dendritic cell (DC) migration and induction of specific T‐cell‐mediated immune responses. DC obtained from PI3Kγ−/− mice showed a reduced ability to respond to chemokines in vitro and ex vivo and to travel to draining lymph nodes under inflammatory conditions. PI3Kγ−/− mice had a selective defect in the number of skin Langerhans cells and in lymph node CD8α − DC. Furthermore, PI3Kγ−/− mice showed a defective capacity to mount contact hypersensitivity and delayed‐type hypersensitivity reactions. This defect was directly related to the reduced ability of antigen‐loaded DC to migrate from the periphery to draining lymph nodes. Thus, PI3Kγ plays a nonredundant role in DC trafficking and in the activation of specific immunity. Therefore, PI3Kγ may be considered a new target to control exaggerated immune reactions.