R-Ras is required for murine dendritic cell maturation and CD4 + T-cell priming

Gobind Singh, Daigo Hashimoto, Xiaocai Yan, Julie Helft, Patricia J.Y. Park, Ge Ma, Rui F. Qiao, Colin R. Kennedy, Shu Hsia Chen, Miriam Merad, Andrew M. Chan*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

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 RRas is expressed by lymphoid and nonlymphoid tissues and drastically upregulated 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-Rasdeficient 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.

Original languageEnglish (US)
Pages (from-to)1693-1701
Number of pages9
JournalBlood
Volume119
Issue number7
DOIs
StatePublished - Feb 16 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Singh, G., Hashimoto, D., Yan, X., Helft, J., Park, P. J. Y., Ma, G., Qiao, R. F., Kennedy, C. R., Chen, S. H., Merad, M., & Chan, A. M. (2012). R-Ras is required for murine dendritic cell maturation and CD4 + T-cell priming. Blood, 119(7), 1693-1701. https://doi.org/10.1182/blood-2011-05-357319