Proceedings of the National Academy of Sciences of the United States of America · 2010
Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Koduru Suresh, Kumar Lalit, Massaad Michel J, Ramesh Narayanaswamy, Le Bras Séverine, Ozcan Esra, Oyoshi Michiko K, Kaku Mayumi, Fujiwara Yuko, Kremer Leonor, King Sandra, Fuhlbrigge Robert, Rodig Scott, Sage Peter, Carman Chris, Alcaide Pilar, Luscinskas Francis W, Geha Raif S
Аннотация
The F-BAR domain containing protein CIP4 (Cdc42 interacting protein 4) interacts with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of filamentous actin. CIP4(-/-) mice had normal T- and B-lymphocyte development but impaired T cell-dependent antibody production, IgG antibody affinity maturation, and germinal center (GC) formation, despite an intact CD40L-CD40 axis. CIP4(-/-) mice also had impaired contact hypersensitivity (CHS) to haptens, and their T cells failed to adoptively transfer CHS. Ovalbumin-activated CD4(+) effector T cells from CIP4(-/-)/OT-II mice migrated poorly to antigen-challenged skin. Activated CIP4(-/-) T cells exhibited impaired adhesion and polarization on immobilized VCAM-1 and ICAM-1 and defective arrest and transmigration across murine endothelial cell monolayers under shear flow conditions. These results demonstrate an important role for CIP4 in integrin-dependent T cell-dependent antibody responses and GC formation and in integrin-mediated recruitment of effector T cells to cutaneous sites of antigen-driven immune reactions.