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

被引：129

作者：

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

机构：

[1] Univ Brescia, Sect Gen Pathol & Immunol, I-25123 Brescia, Italy

[2] Ist Ric Farmacol Mario Negri, Milan, Italy

[3] Univ Brescia, Dept Pathol, I-25121 Brescia, Italy

[4] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy

[5] Univ Fribourg, CH-1700 Fribourg, Switzerland

[6] Univ Milan, Ctr IDET, Inst Gen Pathol, Milan, Italy

来源：

EMBO JOURNAL | 2004年 / 23卷 / 17期

关键词：

chemokines; chemotaxis; contact hypersensitivity; dendritic cells; PI3K gamma-/- mice;

D O I：

10.1038/sj.emboj.7600361

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3505 / 3515

页数：11

共 62 条

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