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R-Ras is required for murine dendritic cell maturation and CD4+T-cell priming
- Source :
- Blood; February 2012, Vol. 119 Issue: 7 p1693-1701, 9p
- Publication Year :
- 2012
-
Abstract
- R-Ras is a member of the RASsuperfamily 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.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 119
- Issue :
- 7
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs57058194
- Full Text :
- https://doi.org/10.1182/blood-2011-05-357319