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.

Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice

BARBERIS, Laura;HIRSCH, Emilio;
2004

Abstract

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.
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http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=516633&blobtype=pdf
chemokines; chemotaxis; contact hypersensitivity; dendritic cells; PI3Kγ−/− mice
DEL PRETE A; VERMI W; DANDER E; OTERO K; BARBERIS L; LUINI W; BERNASCONI S; SIRONI M; SANTORO A; GARLANDA C; FACCHETTI F; WYMANN MP; VECCHI A; HIRSCH E; MANTOVANI A; SOZZANI S
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/38972
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