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PERSPECTIVE article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1533823
This article is part of the Research Topic The transcriptional and metabolic role of Foxp3 in regulatory T cells View all 3 articles

Elusive Modes of Foxp3 Activity in Versatile Regulatory T Cells

Provisionally accepted
Yongqiang Feng Yongqiang Feng *Minghong He Minghong He
  • St. Jude Children's Research Hospital, Memphis, United States

The final, formatted version of the article will be published soon.

    Foxp3-expressing CD4 regulatory T (Treg) cells play a crucial role in suppressing autoimmunity, tolerating food antigens and commensal microbiota, and maintaining tissue integrity. These multifaceted functions are guided by environmental cues through interconnected signaling pathways.Traditionally, Treg fate and function were believed to be statically determined by the forkhead box protein Foxp3 that directly binds to DNA. However, this model has not been rigorously tested in physiological and pathological conditions where Treg cells adapt their function in response to environmental cues, raising questions about the contribution of Foxp3-dependent gene regulation to their versatility. Recent research indicates that Foxp3 primarily functions as a transcriptional cofactor, whose chromatin interaction is influenced by other DNA-binding proteins that respond to cell activation, stimulation, or differentiation. This new perspective offers an opportunity to reevaluate Foxp3's activity modes in diverse biological contexts. By exploring this paradigm, we aim to unravel the fundamental principles of Treg cell biology.

    Keywords: regulatory T cells, Foxp3, transcription factor, Transcriptional cofactor, DNA binding, Chromatin

    Received: 25 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Feng and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yongqiang Feng, St. Jude Children's Research Hospital, Memphis, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.