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R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding. PLoS One 2015;10(12):e0145218

Date

12/29/2015

Pubmed ID

26710069

Pubmed Central ID

PMC4692399

DOI

10.1371/journal.pone.0145218

Scopus ID

2-s2.0-84957536563   4 Citations

Abstract

The trafficking of T-lymphocytes to peripheral draining lymph nodes is crucial for mounting an adaptive immune response. The role of chemokines in the activation of integrins via Ras-related small GTPases has been well established. R-Ras is a member of the Ras-subfamily of small guanosine-5'-triphosphate-binding proteins and its role in T cell trafficking has been investigated in R-Ras null mice (Rras-/-). An examination of the lymphoid organs of Rras-/- mice revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of Rras-/- mice were more disorganized and less mature than those of wild-type mice. Furthermore, CD4+ and CD8+ T cells from Rras-/- mice had approximately 42% lower surface expression of L-selectin/CD62L. These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in Rras-/- T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, Rras-/- T cells had approximately 14.5% attenuation in binding to intercellular adhesion molecule 1 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient mice that were transfused with Rras-/- T cells showed a significant reduction in disease severity when compared with mice transplanted with wild-type T cells. These findings implicate a role for R-Ras in T cell trafficking in the high endothelial venules during an effective immune response.

Author List

Yan X, Yan M, Guo Y, Singh G, Chen Y, Yu M, Wang D, Hillery CA, Chan AM

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Adhesion
Cell Movement
Cell Proliferation
Chemokine CCL21
Enzyme Activation
Female
Graft vs Host Disease
Intercellular Adhesion Molecule-1
L-Selectin
Lymph Nodes
Lymphocyte Function-Associated Antigen-1
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Protein Binding
Spleen
T-Lymphocytes
ras Proteins
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5