R-ras regulates murine T cell migration and intercellular adhesion molecule-1 binding

Xiaocai Yan, Mingfei Yan, Yihe Guo, Gobind Singh, Yuhong Chen, Mei Yu, Demin Wang, Cheryl A. Hillery, Andrew M. Chan

Research output: Contribution to journalArticle

4 Scopus 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 Rasrelated 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 RRas in T cell trafficking in the high endothelial venules during an effective immune response.

Original languageEnglish (US)
Article numbere0145218
JournalPloS one
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Yan, X., Yan, M., Guo, Y., Singh, G., Chen, Y., Yu, M., ... Chan, A. M. (2015). R-ras regulates murine T cell migration and intercellular adhesion molecule-1 binding. PloS one, 10(12), [e0145218]. https://doi.org/10.1371/journal.pone.0145218