Defective dendritic cell migration and activation of adaptive immunity in PI3Kγ-deficient mice
Copyright policy )Defective dendritic cell migration and activation of adaptive immunity in PI3Kγ-deficient mice
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.
Male, Mice, Knockout, Chemokines, cell migration, Knockout mice; Animals; 1-Phosphatidylinositol 3-Kinase; Dendric cells, T-Lymphocytes, Dendritic Cells, In Vitro Techniques, Dermatitis, Contact, chemokines; chemotaxis; contact hypersensitivity; dendritic cells; PI3Kγ−/− mice, Isoenzymes, Mice, Phosphatidylinositol 3-Kinases, Dendritiic cell, Cell Movement, Langerhans Cells, Animals, Class Ib Phosphatidylinositol 3-Kinase, Hypersensitivity, Delayed, Chemokines
Male, Mice, Knockout, Chemokines, cell migration, Knockout mice; Animals; 1-Phosphatidylinositol 3-Kinase; Dendric cells, T-Lymphocytes, Dendritic Cells, In Vitro Techniques, Dermatitis, Contact, chemokines; chemotaxis; contact hypersensitivity; dendritic cells; PI3Kγ−/− mice, Isoenzymes, Mice, Phosphatidylinositol 3-Kinases, Dendritiic cell, Cell Movement, Langerhans Cells, Animals, Class Ib Phosphatidylinositol 3-Kinase, Hypersensitivity, Delayed, Chemokines
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