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Article

  • The EMBO Journal (2004) 23, 3505 - 3515
  • doi:10.1038/sj.emboj.7600361

Published online: 19 August 2004

Defective dendritic cell migration and activation of adaptive immunity in PI3Kbig gamma-deficient mice

Annalisa Del Prete1,a, William Vermi2, Erica Dander1, Karel Otero1, Laura Barberis3, Walter Luini1, Sergio Bernasconi1, Marina Sironi1, Amerigo Santoro2, Cecilia Garlanda1, Fabio Facchetti2, Matthias P Wymann4, Annunciata Vecchi1, Emilio Hirsch3, Alberto Mantovani1,5 and Silvano Sozzani1,6

  1. Istituto Ricerche Farmacologiche 'Mario Negri', Milan, Italy
  2. Department of Pathology, University of Brescia, Italy
  3. Department of Genetic, Biology and Biochemistry, University of Turin, Turin, Italy
  4. University of Fribourg, Fribourg, Switzerland
  5. Centro IDET, Institute of General Pathology, University of Milan, Milan, Italy
  6. Section of General Pathology and Immunology, University of Brescia, Brescia, Italy

Correspondence to:

Silvano Sozzani, Section of General Pathology and Immunology, University of Brescia, viale Europa 11, 25123 Brescia, Italy. Tel.: +39 030 371 7282; Fax: +39 030 370 1157; E-mail: sozzani@med.unibs.it

aPresent address: Section of Medical Biochemistry, University of Bari, Bari, Italy

Received 12 March 2004; Accepted 16 July 2004

Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses. DC obtained from PI3Kgamma-/- mice showed a reduced ability to respond to chemokines in vitro and ex vivo and to travel to draining lymph nodes under inflammatory conditions. PI3Kgamma-/- mice had a selective defect in the number of skin Langerhans cells and in lymph node CD8alpha- DC. Furthermore, PI3Kgamma-/- 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, PI3Kgamma plays a nonredundant role in DC trafficking and in the activation of specific immunity. Therefore, PI3Kgamma may be considered a new target to control exaggerated immune reactions.

  • Keywords:

    • chemokines,
    • chemotaxis,
    • contact hypersensitivity,
    • dendritic cells,
    • PI3Kgamma-/- mice