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Front Immunol. 2019 Oct 18;10:2486. doi: 10.3389/fimmu.2019.02486. eCollection 2019.

Foxp3 Post-translational Modifications and Treg Suppressive Activity.

Author information

1
Department of Immunology, Peking University Health Science Center, Beijing, China.
2
State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
3
Seishin Medical Group, Takara Clinic, Tokyo, Japan.
4
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
5
Centre of Excellence in Translational Immunology (CETI), Research Institute of the McGill University Health Centre, Montréal, QC, Canada.
6
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Abstract

Regulatory T cells (Tregs) are engaged in maintaining immune homeostasis and preventing autoimmunity. Treg cells include thymic Treg cells and peripheral Treg cells, both of which can suppress the immune response via multiple distinct mechanisms. The differentiation, proliferation, suppressive function and survival of Treg cells are affected by distinct energy metabolic programs. Tissue-resident Treg cells hold unique features in comparison with the lymphoid organ Treg cells. Foxp3 transcription factor is a lineage master regulator for Treg cell development and suppressive activity. Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation. These modifications affect multiple aspects of Foxp3 function. In this review, we define features of Treg cells and roles of Foxp3 in Treg biology, and summarize current research in PTMs of Foxp3 protein involved in modulating Treg function. This review also attempts to define Foxp3 dimer modifications relevant to mediating Foxp3 activity and Treg suppression. Understanding Foxp3 protein features and modulation mechanisms may help in the design of rational therapies for immune diseases and cancer.

KEYWORDS:

Foxp3; O-GlcNAcylation; acetylation; methylation; phosphorylation; post-translational modification; regulatory T cells; ubiquitylation

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