The Ras/MAPK pathway is required for generation of iNKT cells.

iNKT cells derive from CD4(+)CD8(+) DP thymocytes, and are selected by thymocyte-thymocyte interactions through signals from their invariant Vα14-Jα18 TCR and from the costimulatory molecules SLAMF1 and SLAMF6. Genetic studies have demonstrated the contribution of different signaling pathways to thi...

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Main Authors: Taishan Hu, Idoia Gimferrer, Amie Simmons, David Wiest, José Alberola-Ila
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-05-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019890&type=printable
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author Taishan Hu
Idoia Gimferrer
Amie Simmons
David Wiest
José Alberola-Ila
author_facet Taishan Hu
Idoia Gimferrer
Amie Simmons
David Wiest
José Alberola-Ila
author_sort Taishan Hu
collection DOAJ
description iNKT cells derive from CD4(+)CD8(+) DP thymocytes, and are selected by thymocyte-thymocyte interactions through signals from their invariant Vα14-Jα18 TCR and from the costimulatory molecules SLAMF1 and SLAMF6. Genetic studies have demonstrated the contribution of different signaling pathways to this process. Surprisingly, current models imply that the Ras/MAPK pathway, one of the critical mediators of conventional αβ T cell positive selection, is not necessary for iNKT cell development. Using mice defective at different levels of this pathway our results refute this paradigm, and demonstrate that Ras, and its downstream effectors Egr-1 and Egr-2 are required for positive selection of iNKT cells. Interestingly our results also show that there are differences in the contributions of several of these molecules to the development of iNKT and conventional αβ T cells.
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institution OA Journals
issn 1932-6203
language English
publishDate 2011-05-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-af8484bcbb5c43019e96be9aa23beb772025-08-20T02:08:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-05-0165e1989010.1371/journal.pone.0019890The Ras/MAPK pathway is required for generation of iNKT cells.Taishan HuIdoia GimferrerAmie SimmonsDavid WiestJosé Alberola-IlaiNKT cells derive from CD4(+)CD8(+) DP thymocytes, and are selected by thymocyte-thymocyte interactions through signals from their invariant Vα14-Jα18 TCR and from the costimulatory molecules SLAMF1 and SLAMF6. Genetic studies have demonstrated the contribution of different signaling pathways to this process. Surprisingly, current models imply that the Ras/MAPK pathway, one of the critical mediators of conventional αβ T cell positive selection, is not necessary for iNKT cell development. Using mice defective at different levels of this pathway our results refute this paradigm, and demonstrate that Ras, and its downstream effectors Egr-1 and Egr-2 are required for positive selection of iNKT cells. Interestingly our results also show that there are differences in the contributions of several of these molecules to the development of iNKT and conventional αβ T cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019890&type=printable
spellingShingle Taishan Hu
Idoia Gimferrer
Amie Simmons
David Wiest
José Alberola-Ila
The Ras/MAPK pathway is required for generation of iNKT cells.
PLoS ONE
title The Ras/MAPK pathway is required for generation of iNKT cells.
title_full The Ras/MAPK pathway is required for generation of iNKT cells.
title_fullStr The Ras/MAPK pathway is required for generation of iNKT cells.
title_full_unstemmed The Ras/MAPK pathway is required for generation of iNKT cells.
title_short The Ras/MAPK pathway is required for generation of iNKT cells.
title_sort ras mapk pathway is required for generation of inkt cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019890&type=printable
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