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R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding
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’-triphos...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692399/ https://www.ncbi.nlm.nih.gov/pubmed/26710069 http://dx.doi.org/10.1371/journal.pone.0145218 |
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author | Yan, Xiaocai Yan, Mingfei Guo, Yihe Singh, Gobind Chen, Yuhong Yu, Mei Wang, Demin Hillery, Cheryl A. Chan, Andrew M. |
author_facet | Yan, Xiaocai Yan, Mingfei Guo, Yihe Singh, Gobind Chen, Yuhong Yu, Mei Wang, Demin Hillery, Cheryl A. Chan, Andrew M. |
author_sort | Yan, Xiaocai |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4692399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46923992016-01-12 R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding Yan, Xiaocai Yan, Mingfei Guo, Yihe Singh, Gobind Chen, Yuhong Yu, Mei Wang, Demin Hillery, Cheryl A. Chan, Andrew M. PLoS One Research Article 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. Public Library of Science 2015-12-28 /pmc/articles/PMC4692399/ /pubmed/26710069 http://dx.doi.org/10.1371/journal.pone.0145218 Text en © 2015 Yan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yan, Xiaocai Yan, Mingfei Guo, Yihe Singh, Gobind Chen, Yuhong Yu, Mei Wang, Demin Hillery, Cheryl A. Chan, Andrew M. R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding |
title | R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding |
title_full | R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding |
title_fullStr | R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding |
title_full_unstemmed | R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding |
title_short | R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding |
title_sort | r-ras regulates murine t cell migration and intercellular adhesion molecule-1 binding |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692399/ https://www.ncbi.nlm.nih.gov/pubmed/26710069 http://dx.doi.org/10.1371/journal.pone.0145218 |
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