title: R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming.
abstract: R-Ras is a member of the RAS superfamily of small GTP-binding proteins. The physiologic function of R-Ras has not been fully elucidated. We found that R-Ras is expressed by lymphoid and nonlymphoid tissues and drastically up-regulated when bone marrow progenitors are induced to differentiate into dendritic cells (DCs). To address the role of R-Ras in DC functions, we generated a R-Ras-deficient mouse strain. We found that tumors induced in Rras(-/-) mice formed with shorter latency and attained greater tumor volumes. This finding has prompted the investigation of a role for R-Ras in the immune system. Indeed, Rras(-/-) mice were impaired in their ability to prime allogeneic and antigen-specific T-cell responses. Rras(-/-) DCs expressed lower levels of surface MHC class II and CD86 in response to lipopolysaccharide compared with wild-type DCs. This was correlated with a reduced phosphorylation of p38 and Akt. Consistently, R-Ras-GTP level was increased within 10 minutes of lipopolysaccharide stimulation. Furthermore, Rras(-/-) DCs have attenuated capacity to spread on fibronectin and form stable immunologic synapses with T cells. Altogether, these findings provide the first demonstration of a role for R-Ras in cell-mediated immunity and further expand on the complexity of small G-protein signaling in DCs.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Gobind
authors.initials: G
authors.lastname: Singh
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Xiaocai
authors.initials: X
authors.lastname: Yan
authors.forename: Julie
authors.initials: J
authors.lastname: Helft
authors.forename: Patricia J-Y
authors.initials: PJ
authors.lastname: Park
authors.forename: Ge
authors.initials: G
authors.lastname: Ma
authors.forename: Rui F
authors.initials: RF
authors.lastname: Qiao
authors.forename: Colin R
authors.initials: CR
authors.lastname: Kennedy
authors.forename: Shu-Hsia
authors.initials: SH
authors.lastname: Chen
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Chan
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C513254:Rras protein, mouse; D018631:ras Proteins