Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking.
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.
Koduru
Suresh
S
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Kumar
Lalit
L
Massaad
Michel J
MJ
Ramesh
Narayanaswamy
N
Le Bras
Séverine
S
Ozcan
Esra
E
Oyoshi
Michiko K
MK
Kaku
Mayumi
M
Fujiwara
Yuko
Y
Kremer
Leonor
L
King
Sandra
S
Fuhlbrigge
Robert
R
Rodig
Scott
S
Sage
Peter
P
Carman
Chris
C
Alcaide
Pilar
P
Luscinskas
Francis W
FW
Geha
Raif S
RS
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology; D016023:Integrins / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000276:immunology*; D015778:Minor Histocompatibility Antigens; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D016023:Integrins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C485787:Trip10 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
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