Elusive modes of Foxp3 activity in versatile regulatory T cells

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,...

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Main Authors: Minghong He, Yongqiang Feng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1533823/full
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author Minghong He
Yongqiang Feng
author_facet Minghong He
Yongqiang Feng
author_sort Minghong He
collection DOAJ
description 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.
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spelling doaj-art-3dc7261ca94642908fa4385c8ea581b02025-01-15T05:11:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15338231533823Elusive modes of Foxp3 activity in versatile regulatory T cellsMinghong HeYongqiang FengFoxp3-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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1533823/fullregulatory T cellsFoxp3transcription factortranscriptional cofactorDNA bindingchromatin
spellingShingle Minghong He
Yongqiang Feng
Elusive modes of Foxp3 activity in versatile regulatory T cells
Frontiers in Immunology
regulatory T cells
Foxp3
transcription factor
transcriptional cofactor
DNA binding
chromatin
title Elusive modes of Foxp3 activity in versatile regulatory T cells
title_full Elusive modes of Foxp3 activity in versatile regulatory T cells
title_fullStr Elusive modes of Foxp3 activity in versatile regulatory T cells
title_full_unstemmed Elusive modes of Foxp3 activity in versatile regulatory T cells
title_short Elusive modes of Foxp3 activity in versatile regulatory T cells
title_sort elusive modes of foxp3 activity in versatile regulatory t cells
topic regulatory T cells
Foxp3
transcription factor
transcriptional cofactor
DNA binding
chromatin
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1533823/full
work_keys_str_mv AT minghonghe elusivemodesoffoxp3activityinversatileregulatorytcells
AT yongqiangfeng elusivemodesoffoxp3activityinversatileregulatorytcells