Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network.
Regulatory T cells (Treg) are essential for T cell homeostasis and maintenance of peripheral tolerance. They prevent activation of auto-reactive T effector cells (Teff) in the context of autoimmunity and allergy. Otherwise, Treg also inhibit effective immune responses against tumors. Besides a numbe...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4755507?pdf=render |
id |
doaj-f21ed477c60c446fbfa47524dbc9c07a |
---|---|
record_format |
Article |
spelling |
doaj-f21ed477c60c446fbfa47524dbc9c07a2020-11-24T21:54:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014919310.1371/journal.pone.0149193Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network.Andrea TuettenbergSusanne A HahnJohanna MazurAslihan Gerhold-AyJetse ScholmaIris MargAlexander UlgesKazuki SatohTobias BoppJos JooreHelmut JonuleitRegulatory T cells (Treg) are essential for T cell homeostasis and maintenance of peripheral tolerance. They prevent activation of auto-reactive T effector cells (Teff) in the context of autoimmunity and allergy. Otherwise, Treg also inhibit effective immune responses against tumors. Besides a number of Treg-associated molecules such as Foxp3, CTLA-4 or GARP, known to play critical roles in Treg differentiation, activation and function, the involvement of additional regulatory elements is suggested. Herein, kinase activities seem to play an important role in Treg fine tuning. Nevertheless, our knowledge regarding the complex intracellular signaling pathways controlling phenotype and function of Treg is still limited and based on single kinase cascades so far. To gain a more comprehensive insight into the pathways determining Treg function we performed kinome profiling using a phosphorylation-based kinome array in human Treg at different activation stages compared to Teff. Here we have determined intriguing quantitative differences in both populations. Resting and activated Treg showed an altered pattern of CD28-dependent kinases as well as of those involved in cell cycle progression. Additionally, significant up-regulation of distinct kinases such as EGFR or CK2 in activated Treg but not in Teff not only resemble data we obtained in previous studies in the murine system but also suggest that those specific molecular activation patterns can be used for definition of the activation and functional state of human Treg. Taken together, detailed investigation of kinome profiles opens the possibility to identify novel molecular mechanisms for a better understanding of Treg biology but also for development of effective immunotherapies against unwanted T cell responses in allergy, autoimmunity and cancer.http://europepmc.org/articles/PMC4755507?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Tuettenberg Susanne A Hahn Johanna Mazur Aslihan Gerhold-Ay Jetse Scholma Iris Marg Alexander Ulges Kazuki Satoh Tobias Bopp Jos Joore Helmut Jonuleit |
spellingShingle |
Andrea Tuettenberg Susanne A Hahn Johanna Mazur Aslihan Gerhold-Ay Jetse Scholma Iris Marg Alexander Ulges Kazuki Satoh Tobias Bopp Jos Joore Helmut Jonuleit Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. PLoS ONE |
author_facet |
Andrea Tuettenberg Susanne A Hahn Johanna Mazur Aslihan Gerhold-Ay Jetse Scholma Iris Marg Alexander Ulges Kazuki Satoh Tobias Bopp Jos Joore Helmut Jonuleit |
author_sort |
Andrea Tuettenberg |
title |
Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. |
title_short |
Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. |
title_full |
Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. |
title_fullStr |
Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. |
title_full_unstemmed |
Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. |
title_sort |
kinome profiling of regulatory t cells: a closer look into a complex intracellular network. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Regulatory T cells (Treg) are essential for T cell homeostasis and maintenance of peripheral tolerance. They prevent activation of auto-reactive T effector cells (Teff) in the context of autoimmunity and allergy. Otherwise, Treg also inhibit effective immune responses against tumors. Besides a number of Treg-associated molecules such as Foxp3, CTLA-4 or GARP, known to play critical roles in Treg differentiation, activation and function, the involvement of additional regulatory elements is suggested. Herein, kinase activities seem to play an important role in Treg fine tuning. Nevertheless, our knowledge regarding the complex intracellular signaling pathways controlling phenotype and function of Treg is still limited and based on single kinase cascades so far. To gain a more comprehensive insight into the pathways determining Treg function we performed kinome profiling using a phosphorylation-based kinome array in human Treg at different activation stages compared to Teff. Here we have determined intriguing quantitative differences in both populations. Resting and activated Treg showed an altered pattern of CD28-dependent kinases as well as of those involved in cell cycle progression. Additionally, significant up-regulation of distinct kinases such as EGFR or CK2 in activated Treg but not in Teff not only resemble data we obtained in previous studies in the murine system but also suggest that those specific molecular activation patterns can be used for definition of the activation and functional state of human Treg. Taken together, detailed investigation of kinome profiles opens the possibility to identify novel molecular mechanisms for a better understanding of Treg biology but also for development of effective immunotherapies against unwanted T cell responses in allergy, autoimmunity and cancer. |
url |
http://europepmc.org/articles/PMC4755507?pdf=render |
work_keys_str_mv |
AT andreatuettenberg kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT susanneahahn kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT johannamazur kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT aslihangerholday kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT jetsescholma kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT irismarg kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT alexanderulges kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT kazukisatoh kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT tobiasbopp kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT josjoore kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork AT helmutjonuleit kinomeprofilingofregulatorytcellsacloserlookintoacomplexintracellularnetwork |
_version_ |
1725868897556496384 |