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Authors: Tüttenberg, Andrea
Hahn, Susanne A.
Mazur, Johanna
Gerhold-Ay, Aslihan
Scholma, Jetse
Marg, Iris
Ulges, Alexander
Satoh, Kazuki
Bopp, Tobias
Joore, Jos
Jonuleit, Helmut
Title: Kinome profiling of regulatory T cells : a closer look into a complex intracellular network
Online publication date: 15-Sep-2022
Language: english
Abstract: 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.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: PLoS one
Pages or article number: e0149193
Publisher: PLoS
Publisher place: Lawrence, Kan.
Issue date: 2016
ISSN: 1932-6203
Publisher URL:
Publisher DOI: 10.1371/journal.pone.0149193
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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