R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding
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AbstractThe 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.
All Author(s) ListYan XC, Yan MF, Guo YH, Singh G, Chen YH, Yu M, Wang DM, Hillery CA, Chan AM
Journal namePLoS ONE
Volume Number10
Issue Number12
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesMultidisciplinary Sciences; Science & Technology - Other Topics

Last updated on 2020-21-09 at 01:25