Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-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.
Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
Annalisa
A
Del Prete
William
W
Vermi
Erica
E
Dander
Karel
K
Otero
Laura
L
Barberis
Walter
W
Luini
Sergio
S
Bernasconi
Marina
M
Sironi
Amerigo
A
Santoro
Cecilia
C
Garlanda
Fabio
F
Facchetti
Matthias P
MP
Wymann
Annunciata
A
Vecchi
Emilio
E
Hirsch
Alberto
A
Mantovani
Silvano
S
Sozzani
D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000494:pharmacology; D058544:Class Ib Phosphatidylinositol 3-Kinase; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D003877:Dermatitis, Contact; D006968:Hypersensitivity, Delayed; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D018925:Chemokines; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse