An Increase in Tolerogenic Dendritic Cell and Natural T Regulatory Cell Numbers During EAE in Rras−/− Mice Results in Attenuated Disease

• Published in: The Journal of immunology (1950) 2014-04, Vol.192 (11), p.5109-5117
• Main Authors: Ray, Avijit, Basu, Sreemanti, Miller, Nichole M., Chan, Andrew M., Dittel, Bonnie N.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1302254

R-Ras is a member of the Ras superfamily of small GTPases, which are regulators of various cellular processes including adhesion, survival, proliferation, trafficking and cytokine production. R-Ras is expressed by immune cells and has been shown to modulate DC function in vitro and has been associated with liver autoimmunity. We used Rras -deficient mice to study the mechanism whereby R-Ras contributes to autoimmunity using experimental autoimmune encephalomyelitis (EAE), a mouse model of the CNS autoimmune disease multiple sclerosis (MS). We found that a lack of R-Ras in peripheral immune cells resulted in attenuated EAE disease. Further investigation revealed that during EAE, absence of R-Ras promoted the formation of MHC II lo DC concomitant with a significant increase in proliferation of natural T regulatory cells (nTreg) resulting in an increase in their cell numbers in the periphery. Our study suggests a novel role for R-Ras in promoting autoimmunity through negative regulation of nTreg numbers by inhibiting the development of MHCII lo DC with tolerogenic potential.