Treg functional stability and its responsiveness to the microenvironment

Research output: Contribution to journalArticle

Abstract

Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting, and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability.

Original languageEnglish (US)
Pages (from-to)115-139
Number of pages25
JournalImmunological Reviews
Volume259
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Forkhead Transcription Factors
Regulatory T-Lymphocytes
Post Translational Protein Processing
Autoimmunity
Epigenomics
Cues
Transcription Factors
Population

Keywords

  • Foxp3
  • Functional stability
  • Proinflammatory cytokines
  • Treg

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Treg functional stability and its responsiveness to the microenvironment. / Barbi, Joseph; Pardoll, Andrew Mark; Pan, Fan.

In: Immunological Reviews, Vol. 259, No. 1, 2014, p. 115-139.

Research output: Contribution to journalArticle

@article{c0e826c73a0e45259e4e50b7c1f9aa90,
title = "Treg functional stability and its responsiveness to the microenvironment",
abstract = "Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting, and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability.",
keywords = "Foxp3, Functional stability, Proinflammatory cytokines, Treg",
author = "Joseph Barbi and Pardoll, {Andrew Mark} and Fan Pan",
year = "2014",
doi = "10.1111/imr.12172",
language = "English (US)",
volume = "259",
pages = "115--139",
journal = "Immunological Reviews",
issn = "0105-2896",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Treg functional stability and its responsiveness to the microenvironment

AU - Barbi, Joseph

AU - Pardoll, Andrew Mark

AU - Pan, Fan

PY - 2014

Y1 - 2014

N2 - Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting, and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability.

AB - Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting, and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability.

KW - Foxp3

KW - Functional stability

KW - Proinflammatory cytokines

KW - Treg

UR - http://www.scopus.com/inward/record.url?scp=84897952509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897952509&partnerID=8YFLogxK

U2 - 10.1111/imr.12172

DO - 10.1111/imr.12172

M3 - Article

C2 - 24712463

AN - SCOPUS:84897952509

VL - 259

SP - 115

EP - 139

JO - Immunological Reviews

JF - Immunological Reviews

SN - 0105-2896

IS - 1

ER -