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

Alessandra Colamatteo, Fortunata Carbone, Sara Bruzzaniti, Mario Galgani, Clorinda Fusco, Giorgia Teresa Maniscalco, Francesca Di Rella, Paola de Candia, Veronica De Rosa

Research output: Contribution to journalReview article

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.

Original languageEnglish
Article number3136
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - Feb 3 2020

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Keywords

  • autoimmunity
  • epigenetic regulation
  • Foxp3
  • Foxp3 stability
  • Treg cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Colamatteo, A., Carbone, F., Bruzzaniti, S., Galgani, M., Fusco, C., Maniscalco, G. T., Di Rella, F., de Candia, P., & De Rosa, V. (2020). Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation. Frontiers in Immunology, 10, [3136]. https://doi.org/10.3389/fimmu.2019.03136