An increase in tolerogenic dendritic cell and natural regulatory T cell numbers during experimental autoimmune encephalomyelitis in Rras-/- mice results in attenuated disease.

Authors:
Avijit Ray, PhD
Avijit Ray, PhD
AbbVie
Senior Scientist II
Immunology, Immuno-oncology, Autoimmunity and Inflammation, Immune tolerance
North Chicago, IL | United States
Sreemanti Basu
Sreemanti Basu
Blood Research Institute
United States
Nichole M Miller
Nichole M Miller
Blood Research Institute
United States
Andrew M Chan
Andrew M Chan
Mount Sinai School of Medicine
United States
Bonnie N Dittel
Bonnie N Dittel
Blood Research Institute

J Immunol 2014 Jun 25;192(11):5109-17. Epub 2014 Apr 25.

Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226; and

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 dendritic cell (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. 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(low) DC concomitant with a significant increase in proliferation of natural regulatory T cells, 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 natural regulatory T cell numbers by inhibiting the development of MHCII(low) DC with tolerogenic potential.

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Source
http://dx.doi.org/10.4049/jimmunol.1302254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041102PMC

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June 2014
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