RT Journal Article SR Electronic T1 Cutting Edge: Rho Activation and Actin Polarization Are Dependent on Plexin-A1 in Dendritic Cells JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 4271 OP 4275 DO 10.4049/jimmunol.177.7.4271 VO 177 IS 7 A1 Eun, So-Young A1 O’Connor, Brian P. A1 Wong, Athena W. A1 van Deventer, Hendrick W. A1 Taxman, Debra J. A1 Reed, William A1 Li, Ping A1 Blum, Janice S. A1 McKinnon, Karen P. A1 Ting, Jenny P.-Y. YR 2006 UL http://www.jimmunol.org/content/177/7/4271.abstract AB We recently identified expression of the semaphorin receptor, plexin-A1, in dendritic cells (DCs); however, its function in these cells remains to be elucidated. To investigate function and maximize physiological relevance, we devised a retroviral approach to ablate plexin-A1 gene expression using small hairpin RNA (shRNA) in primary bone marrow-derived DCs. We show that plexin-A1 localizes within the cytoplasm of immature DCs, becomes membrane-associated, and is enriched at the immune synapse in mature DCs. Reducing plexin-A1 expression with shRNA greatly reduced actin polarization as well as Rho activation without affecting Rac or Cdc42 activation. A Rho inhibitor, C3, also reduced actin polarization. These changes were accompanied by the near-ablation of T cell activation. We propose a mechanism of adaptive immune regulation in which plexin-A1 controls Rho activation and actin cytoskeletal rearrangements in DCs that is associated with enhanced DC-T cell interactions.