Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking

Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16252-6. doi: 10.1073/pnas.1002747107. Epub 2010 Aug 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cell Adhesion
  • Cell Movement*
  • Cell Polarity
  • Dermatitis, Allergic Contact / genetics
  • Dermatitis, Allergic Contact / immunology
  • Integrins / immunology*
  • Intercellular Adhesion Molecule-1 / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins / deficiency
  • Microtubule-Associated Proteins / immunology*
  • Minor Histocompatibility Antigens
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Vascular Cell Adhesion Molecule-1 / immunology


  • Integrins
  • Microtubule-Associated Proteins
  • Minor Histocompatibility Antigens
  • Trip10 protein, mouse
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1