Article
- The EMBO Journal (2004) 23, 3505 - 3515
- doi:10.1038/sj.emboj.7600361
Published online: 19 August 2004
Subject Categories:
Defective dendritic cell migration and activation of adaptive immunity in PI3K
-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
- Istituto Ricerche Farmacologiche 'Mario Negri', Milan, Italy
- Department of Pathology, University of Brescia, Italy
- Department of Genetic, Biology and Biochemistry, University of Turin, Turin, Italy
- University of Fribourg, Fribourg, Switzerland
- Centro IDET, Institute of General Pathology, University of Milan, Milan, Italy
- 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
Abstract
Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3K
) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses. DC obtained from PI3K-/- mice showed a reduced ability to respond to chemokines in vitro and ex vivo and to travel to draining lymph nodes under inflammatory conditions. PI3K-/- mice had a selective defect in the number of skin Langerhans cells and in lymph node CD8
- DC. Furthermore, PI3K-/- 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, PI3K plays a nonredundant role in DC trafficking and in the activation of specific immunity. Therefore, PI3K may be considered a new target to control exaggerated immune reactions.
Keywords:
- chemokines,
- chemotaxis,
- contact hypersensitivity,
- dendritic cells,
- PI3K-/- mice
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