title: Rho-family GTPase Cdc42 controls migration of Langerhans cells in vivo.
abstract: Epidermal Langerhans cells (LCs) of the skin represent the prototype migratory dendritic cell (DC) subtype. In the skin, they take up Ag, migrate to the draining lymph nodes, and contribute to Ag transport and immunity. Different depletion models for LCs have revealed contrasting roles and contributions of this cell type. To target the migratory properties of DCs, we generated mice lacking the Rho-family GTPase Cdc42 specifically in DCs. In these animals, the initial seeding of the epidermis with LCs is functional, resulting in slightly reduced Langerhans cell numbers. However, Cdc42-deficient LCs fail to leave the skin in steady state as well as upon stimulation, as they do not enter the skin-draining afferent lymph vessels. Similarly, also other Cdc42-deficient migratory DC subsets fail to home properly to the corresponding draining lymph nodes. We used this novel mouse model, in which LCs are locked out, to demonstrate that these cells contribute substantially to priming of Ag-specific CD4 and CD8 T cell responses upon epicutaneous immunization, but could not detect a role in the induction of contact hypersensitivity to various doses of hapten.
authors.affiliation: Institute for Immunology, Ludwig-Maximilians-University, D-80336 Munich, Germany.
authors.forename: Nancy
authors.initials: N
authors.lastname: Luckashenak
authors.forename: Anna
authors.initials: A
authors.lastname: Wähe
authors.forename: Katharina
authors.initials: K
authors.lastname: Breit
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Thomas
authors.initials: T
authors.lastname: Brocker
mesh_terms: D000818:Animals; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007801:Langerhans Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D020764:cdc42 GTP-Binding Protein