Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation: Frontiers in Immunology

A. Colamatteo; F. Carbone; S. Bruzzaniti; M. Galgani; C. Fusco; G.T. Maniscalco; F. Di Rella; P. de Candia; V. De Rosa

doi:10.3389/fimmu.2019.03136

Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation: Frontiers in Immunology

A. Colamatteo, F. Carbone, S. Bruzzaniti, M. Galgani, C. Fusco, G.T. Maniscalco, F. Di Rella, P. de Candia, V. De Rosa

IRCCS Multimedica

Research output: Contribution to journal › Article › peer-review

Abstract

The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+ T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. © Copyright © 2020 Colamatteo, Carbone, Bruzzaniti, Galgani, Fusco, Maniscalco, Di Rella, de Candia and De Rosa.

Original language	English
Journal	Front. Immunol.
Volume	10
DOIs	https://doi.org/10.3389/fimmu.2019.03136
Publication status	Published - 2020

Keywords

autoimmunity
epigenetic regulation
Foxp3
Foxp3 stability
Treg cells
histone
microRNA
transcription factor FOXP3
forkhead transcription factor
FOXP3 protein, human
autoimmune disease
cell fate
cell function
cell plasticity
epigenetics
gene expression
gene locus
human
inflammation
protein processing
protein stability
regulatory T lymphocyte
Review
transcription regulation
animal
biosynthesis
cell differentiation
gene expression regulation
genetic epigenesis
genetics
immunology
metabolism
physiology
T lymphocyte subpopulation
Animals
Autoimmunity
Cell Differentiation
Epigenesis, Genetic
Forkhead Transcription Factors
Gene Expression Regulation
Humans
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory

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Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation : Frontiers in Immunology. / Colamatteo, A.; Carbone, F.; Bruzzaniti, S.; Galgani, M.; Fusco, C.; Maniscalco, G.T.; Di Rella, F.; de Candia, P.; De Rosa, V.

In: Front. Immunol., Vol. 10, 2020.

Research output: Contribution to journal › Article › peer-review

@article{c2eb96d61ba34c65a62312b61f20bb68,

title = "Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation: Frontiers in Immunology",

abstract = "The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+ T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. {\textcopyright} Copyright {\textcopyright} 2020 Colamatteo, Carbone, Bruzzaniti, Galgani, Fusco, Maniscalco, Di Rella, de Candia and De Rosa.",

keywords = "autoimmunity, epigenetic regulation, Foxp3, Foxp3 stability, Treg cells, histone, microRNA, transcription factor FOXP3, forkhead transcription factor, FOXP3 protein, human, autoimmune disease, cell fate, cell function, cell plasticity, epigenetics, gene expression, gene locus, human, inflammation, protein processing, protein stability, regulatory T lymphocyte, Review, transcription regulation, animal, biosynthesis, cell differentiation, gene expression regulation, genetic epigenesis, genetics, immunology, metabolism, physiology, T lymphocyte subpopulation, Animals, Autoimmunity, Cell Differentiation, Epigenesis, Genetic, Forkhead Transcription Factors, Gene Expression Regulation, Humans, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory",

author = "A. Colamatteo and F. Carbone and S. Bruzzaniti and M. Galgani and C. Fusco and G.T. Maniscalco and {Di Rella}, F. and {de Candia}, P. and {De Rosa}, V.",

note = "Cited By :5 Export Date: 5 March 2021 Correspondence Address: De Rosa, V.; Laboratorio di Immunologia, Italy; email: veronica.derosa@cnr.it Chemicals/CAS: histone, 9062-68-4; Forkhead Transcription Factors; FOXP3 protein, human Funding details: PP-1606-24687, PP-1804-30725 Funding details: National Multiple Sclerosis Society Funding details: Universit{\`a} degli Studi di Napoli Federico II, UNINA Funding details: Fondazione Italiana Sclerosi Multipla, FISM, 2016/R/10, 2018/R/4 Funding details: Compagnia di San Paolo Funding details: Juvenile Diabetes Research Foundation United States of America, JDRF, 1-SRA-2018-477-S-B, 2-SRA-2018-479-S-B Funding details: Juvenile Diabetes Research Foundation Australia Funding details: Ministero della Salute, GR-2016-02363725 Funding text 1: This paper was supported by grants from Fondazione Italiana Sclerosi Multipla (FISM no. 2018/R/4 to VD, and no. 2016/R/10 to PC), Ministero della Salute grant (no. GR-2016-02363725) to VD and FC, the Universit{\`a} degli Studi di Napoli Federico II (STAR Program Linea 1−2018 funded by UniNA and Compagnia di San Paolo) to VD, the Juvenile Diabetes Research Foundation (JDRF no. 2-SRA-2018-479-S-B to MG and no. 1-SRA-2018-477-S-B to PC), and the National Multiple Sclerosis Society (NMSS no. PP-1804-30725 to MG and PP-1606-24687 to PC). Part of images used in the figure preparation was from the Motifolio drawing toolkits (www.motifolio.com). 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year = "2020",

doi = "10.3389/fimmu.2019.03136",

language = "English",

volume = "10",

journal = "Front. Immunol.",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

T2 - Frontiers in Immunology

AU - Colamatteo, A.

AU - Carbone, F.

AU - Bruzzaniti, S.

AU - Galgani, M.

AU - Fusco, C.

AU - Maniscalco, G.T.

AU - Di Rella, F.

AU - de Candia, P.

AU - De Rosa, V.

N1 - Cited By :5 Export Date: 5 March 2021 Correspondence Address: De Rosa, V.; Laboratorio di Immunologia, Italy; email: veronica.derosa@cnr.it Chemicals/CAS: histone, 9062-68-4; Forkhead Transcription Factors; FOXP3 protein, human Funding details: PP-1606-24687, PP-1804-30725 Funding details: National Multiple Sclerosis Society Funding details: Università degli Studi di Napoli Federico II, UNINA Funding details: Fondazione Italiana Sclerosi Multipla, FISM, 2016/R/10, 2018/R/4 Funding details: Compagnia di San Paolo Funding details: Juvenile Diabetes Research Foundation United States of America, JDRF, 1-SRA-2018-477-S-B, 2-SRA-2018-479-S-B Funding details: Juvenile Diabetes Research Foundation Australia Funding details: Ministero della Salute, GR-2016-02363725 Funding text 1: This paper was supported by grants from Fondazione Italiana Sclerosi Multipla (FISM no. 2018/R/4 to VD, and no. 2016/R/10 to PC), Ministero della Salute grant (no. GR-2016-02363725) to VD and FC, the Università degli Studi di Napoli Federico II (STAR Program Linea 1−2018 funded by UniNA and Compagnia di San Paolo) to VD, the Juvenile Diabetes Research Foundation (JDRF no. 2-SRA-2018-479-S-B to MG and no. 1-SRA-2018-477-S-B to PC), and the National Multiple Sclerosis Society (NMSS no. PP-1804-30725 to MG and PP-1606-24687 to PC). Part of images used in the figure preparation was from the Motifolio drawing toolkits (www.motifolio.com). 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PY - 2020

Y1 - 2020

N2 - The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+ T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. © Copyright © 2020 Colamatteo, Carbone, Bruzzaniti, Galgani, Fusco, Maniscalco, Di Rella, de Candia and De Rosa.

AB - The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+ T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. © Copyright © 2020 Colamatteo, Carbone, Bruzzaniti, Galgani, Fusco, Maniscalco, Di Rella, de Candia and De Rosa.

KW - autoimmunity

KW - epigenetic regulation

KW - Foxp3

KW - Foxp3 stability

KW - Treg cells

KW - histone

KW - microRNA

KW - transcription factor FOXP3

KW - forkhead transcription factor

KW - FOXP3 protein, human

KW - autoimmune disease

KW - cell fate

KW - cell function

KW - cell plasticity

KW - epigenetics

KW - gene expression

KW - gene locus

KW - human

KW - inflammation

KW - protein processing

KW - protein stability

KW - regulatory T lymphocyte

KW - Review

KW - transcription regulation

KW - animal

KW - biosynthesis

KW - cell differentiation

KW - gene expression regulation

KW - genetic epigenesis

KW - genetics

KW - immunology

KW - metabolism

KW - physiology

KW - T lymphocyte subpopulation

KW - Animals

KW - Autoimmunity

KW - Cell Differentiation

KW - Epigenesis, Genetic

KW - Forkhead Transcription Factors

KW - Gene Expression Regulation

KW - Humans

KW - T-Lymphocyte Subsets

KW - T-Lymphocytes, Regulatory

U2 - 10.3389/fimmu.2019.03136

DO - 10.3389/fimmu.2019.03136

M3 - Article

VL - 10

JO - Front. Immunol.

JF - Front. Immunol.

SN - 1664-3224

ER -