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

Annalisa Del Prete, William Vermi, Erica Dander, Karel Otero, Laura Barberis, Walter Luini, Sergio Bernasconi, Marina Sironi, Amerigo Santoro, Cecilia Garlanda, Fabio Faccheti, Matthias P. Wymann, Annunciata Vecchi, Emilio Hirsch, Alberto Mantovani, Silvano Sozzani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3505-3515
Number of pages11
JournalEMBO Journal
Volume23
Issue number17
DOIs
Publication statusPublished - Sep 1 2004

Keywords

  • Chemokines
  • Chemotaxis
  • Contact hypersensitivity
  • Dendritic cells
  • PI3Kγ-/- mice

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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  • Cite this

    Del Prete, A., Vermi, W., Dander, E., Otero, K., Barberis, L., Luini, W., Bernasconi, S., Sironi, M., Santoro, A., Garlanda, C., Faccheti, F., Wymann, M. P., Vecchi, A., Hirsch, E., Mantovani, A., & Sozzani, S. (2004). Defective dendritic cell migration and activation of adaptive immunity in PI3Kγ-deficient mice. EMBO Journal, 23(17), 3505-3515. https://doi.org/10.1038/sj.emboj.7600361