Cargando…

First Insight into the Kinome of Human Regulatory T Cells

Regulatory T cells (Tregs) are essential for controlling peripheral tolerance by the active suppression of various immune cells including conventional T effector cells (Teffs). Downstream of the T cell receptor (TCR), more than 500 protein kinases encoded by the human genome have to be considered in...

Descripción completa

Detalles Bibliográficos
Autores principales: König, Sebastian, Probst-Kepper, Michael, Reinl, Tobias, Jeron, Andreas, Huehn, Jochen, Schraven, Burkhart, Jänsch, Lothar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397934/
https://www.ncbi.nlm.nih.gov/pubmed/22815858
http://dx.doi.org/10.1371/journal.pone.0040896
_version_ 1782238213360844800
author König, Sebastian
Probst-Kepper, Michael
Reinl, Tobias
Jeron, Andreas
Huehn, Jochen
Schraven, Burkhart
Jänsch, Lothar
author_facet König, Sebastian
Probst-Kepper, Michael
Reinl, Tobias
Jeron, Andreas
Huehn, Jochen
Schraven, Burkhart
Jänsch, Lothar
author_sort König, Sebastian
collection PubMed
description Regulatory T cells (Tregs) are essential for controlling peripheral tolerance by the active suppression of various immune cells including conventional T effector cells (Teffs). Downstream of the T cell receptor (TCR), more than 500 protein kinases encoded by the human genome have to be considered in signaling cascades regulating the activation of Tregs and Teffs, respectively. Following TCR engagement, Tregs posses a number of unique attributes, such as constitutive expression of Foxp3, hyporesponsiveness and poor cytokine production. Furthermore, recent studies showed that altered regulation of protein kinases is important for Treg function. These data indicate that signaling pathways in Tregs are distinctly organized and alterations at the level of protein kinases contribute to the unique Treg phenotype. However, kinase-based signaling networks in Tregs are poorly understood and necessitate further systematic characterization. In this study, we analyzed the differential expression of kinases in Tregs and Teffs by using a kinase-selective proteome strategy. In total, we revealed quantitative information on 185 kinases expressed in the human CD4(+) T cell subsets. The majority of kinases was equally abundant in both T cell subsets, but 11 kinases were differentially expressed in Tregs. Most strikingly, Tregs showed an altered expression of cell cycle kinases including CDK6. Quantitative proteomics generates first comparative insight into the kinase complements of the CD4(+) Teff and Treg subset. Treg-specific expression pattern of 11 protein kinases substantiate the current opinion that TCR-mediated signaling cascades are altered in Tregs and further suggests that Tregs exhibit significant specificities in cell-cycle control and progression.
format Online
Article
Text
id pubmed-3397934
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-33979342012-07-19 First Insight into the Kinome of Human Regulatory T Cells König, Sebastian Probst-Kepper, Michael Reinl, Tobias Jeron, Andreas Huehn, Jochen Schraven, Burkhart Jänsch, Lothar PLoS One Research Article Regulatory T cells (Tregs) are essential for controlling peripheral tolerance by the active suppression of various immune cells including conventional T effector cells (Teffs). Downstream of the T cell receptor (TCR), more than 500 protein kinases encoded by the human genome have to be considered in signaling cascades regulating the activation of Tregs and Teffs, respectively. Following TCR engagement, Tregs posses a number of unique attributes, such as constitutive expression of Foxp3, hyporesponsiveness and poor cytokine production. Furthermore, recent studies showed that altered regulation of protein kinases is important for Treg function. These data indicate that signaling pathways in Tregs are distinctly organized and alterations at the level of protein kinases contribute to the unique Treg phenotype. However, kinase-based signaling networks in Tregs are poorly understood and necessitate further systematic characterization. In this study, we analyzed the differential expression of kinases in Tregs and Teffs by using a kinase-selective proteome strategy. In total, we revealed quantitative information on 185 kinases expressed in the human CD4(+) T cell subsets. The majority of kinases was equally abundant in both T cell subsets, but 11 kinases were differentially expressed in Tregs. Most strikingly, Tregs showed an altered expression of cell cycle kinases including CDK6. Quantitative proteomics generates first comparative insight into the kinase complements of the CD4(+) Teff and Treg subset. Treg-specific expression pattern of 11 protein kinases substantiate the current opinion that TCR-mediated signaling cascades are altered in Tregs and further suggests that Tregs exhibit significant specificities in cell-cycle control and progression. Public Library of Science 2012-07-16 /pmc/articles/PMC3397934/ /pubmed/22815858 http://dx.doi.org/10.1371/journal.pone.0040896 Text en König 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
König, Sebastian
Probst-Kepper, Michael
Reinl, Tobias
Jeron, Andreas
Huehn, Jochen
Schraven, Burkhart
Jänsch, Lothar
First Insight into the Kinome of Human Regulatory T Cells
title First Insight into the Kinome of Human Regulatory T Cells
title_full First Insight into the Kinome of Human Regulatory T Cells
title_fullStr First Insight into the Kinome of Human Regulatory T Cells
title_full_unstemmed First Insight into the Kinome of Human Regulatory T Cells
title_short First Insight into the Kinome of Human Regulatory T Cells
title_sort first insight into the kinome of human regulatory t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397934/
https://www.ncbi.nlm.nih.gov/pubmed/22815858
http://dx.doi.org/10.1371/journal.pone.0040896
work_keys_str_mv AT konigsebastian firstinsightintothekinomeofhumanregulatorytcells
AT probstkeppermichael firstinsightintothekinomeofhumanregulatorytcells
AT reinltobias firstinsightintothekinomeofhumanregulatorytcells
AT jeronandreas firstinsightintothekinomeofhumanregulatorytcells
AT huehnjochen firstinsightintothekinomeofhumanregulatorytcells
AT schravenburkhart firstinsightintothekinomeofhumanregulatorytcells
AT janschlothar firstinsightintothekinomeofhumanregulatorytcells